[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.

[The efficacy and safety of intra-articular application of a combination of sodium hyaluronate and chondroitin sulfate for osteoarthritis of the knee: a multicenter prospective study].

in 3 mL on patients with knee osteoarthritis (OA) in a multicenter prospective study. MATERIALS AND METHODS: 79 outpatients (predominantly females 81.0%) from 5 RF constituent territories with primary tibiofemoral KellgrenLawrence score grade II or III knee OA, 40 mm pain intensity during walking on visual analogue scale (VAS), requiring NSAIDs intake (for at least 30 days during 3 months prior to enrollment) were included into the study after signing the informed consent form. Mean age was 60.38.7 years, mean BMI 29.24.7 kg/m2, disease duration 6 (310) years. Grade II OA was documented in 68.4% of patients, Grade III in 31.6%. The study lasted for 6 months. Efficacy and safety evaluations were made based on VAS pain assessment, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [WOMAC pain (0500), WOMAC function (01700), WOMAC stiffness (0200)], VAS patients health status, EQ-5D-based assessment of patients quality of life, global physicians and patients efficacy assessment, and daily NSAIDs requirements. RESULTS: Obtained results demonstrate statistically significant VAS pain reduction during walking already in 1 week after intra-articular injection of the combination [respectively, 62 (5572) and 41 (3251) mm, р0.0001]. Moreover, pain continued to subside during all 3 months of follow up [in 1 month 28 (2042), in 3 month 22 (1437) mm]. A significant pan reduction achieved at Mo 3 persisted until Mo 6 20 (1442) mm, without documented pain increase. Similar trends were observed with total WOMAC score [1125 (8991540) at baseline, and 552 (309837) mm by the end of the study, p0.0001], and all WOMAC sub-scores [268 (189312) baseline WOMAC pain, 91 (48171) mm by the end of the study p0.0001; stiffness 101 (59130) and 40 (2061) mm, p0.0001; function 802 (6471095) and 402 (191638) mm, p0.0001, respectively]. Median time to the onset of therapeutic effect was 7 (518) days. Statistically significant improvement of patients quality of life by EQ-5D and general health status was observed during all follow up period [respectively, 0.52 (-0.020.59) and 0.69 (0.590.80), р0.0001; 48 (3060) and 72 (6080) mm, р0.0001]. One injection of the drug resulted in dose reduction or discontinuation of NSAIDs therapy: at baseline 76 patients (96.2%) were taking NSAIDs, in one week 31 (39.2%) patients discontinued NSAIDs, in 1 month 72.2%, in 3 months 73.4%, and by the end of the study at Mo 6 54.4% were not taking NSAIDs. These data were consistent with physicians and patients global assessment of the efficacy of treatment, who stated significant improvement and improvement in the majority of cases, with only few no effect or worsening cases documented in analyzed population. Adverse events, such as worsening of pain and/or swelling of the joint, were documented in 8 patients (10.1%); they resolved spontaneously or following NSAIDs intake. CONCLUSION: These results suggest that intra-articular injections of hyaluronic acid plus chondroitin sulfate in patients with knee OA are efficient and safe. A single injection of the drug resulted in statistically significant reduction of pain and stiffness, reduction in NSAIDs intake, as well as improvement in patients quality of life and function.

[The combination of chondroitin sulfate and glucosamine (artra) for pain relief and to reduce the consumption of NSAIDs in patients with I-II stages of osteoarthritis of the knee].

The analysis of the dynamics of pain and joint function on the background of the 3-month ARTRA.Study was conducted as a multicenter, with the inclusion of 3077 patients, 56.2% of whom received NSAIDs for pain relief. While taking after a month of therapy showed significant compared to the original value of reducing the intensity of pain. The therapeutic effect is increased with duration of dosing. It is shown that the drug reduces the need for arthritis NSAIDs after a month by 6.8%, after 3 months - by 37.3%, ie after the 3-month course of treatment with arthritis, the number of people taking NSAIDs fell by more than 3 times (up 18.9%). A significant reduction in consumption, coupled with the marked dynamics of the pain is regarded by us as a manifestation expressed anesthetic effect of the drug ARTRA.

[Smoking and alcohol abuse, risk factors of aseptic instability of hip endoprostheses].

Effect of smoking and alcohol abuse as risk factors of aseptic instability of endoprostheses was evaluated from mass dynamics of bone tissue bordering the grafts. The assessments were made in 188 patients during the period of adaptive restructuring of the bone tissue, i.e., within 15 months after surgery. Smoking and alcohol abuse were shown to slow down adequate increment of bone tissue mass in the proximal Gruen's zones during the second phase of restructuring. Patients of either sex failed to regenerate the tissue lost in the stress-shielding period unlike subjects of the control group. Moreover, the deficiency of bone tissue mass in these zones persisted within 15 months after surgery. Adverse effect of smoking on the initial conditions of bone tissue was more pronounced in men than in women. The reverse was true as far as the alcohol effect is concerned. Poor recovery of bone tissue mass around the endoprosthesis enhances its micromobility and may be a cause of its aseptic instability.

[Efficacy and safety of bivalos therapy for postmenopausal osteoporosis. Results of Russian multicenter trial].

AIM: To study effects of one-year therapy with bivalos on mineral bone density (MBD) of the spine in patients with postmenopausal osteoporosis (PMO), effects of bivalos (strontium ranelate) on MBD of the neck of the femur and femur, the levels of bone metabolism markers, quality of life, tolerance of long-term therapy. MATERIAL AND METHODS: The study was made of 60 females aged 54-75 years with PMO. MBD was measured with x-ray absorptiometry in the vertebra and proximal femur. Bone markers in blood serum were detected by enzyme immunoassay. RESULTS: After a year of taking bivalos MBD in lumbar vertebra increased by 4.68 +/- 4.94%, in the neck of the femur--by 2.0 +/- 4.29%, in the proximal femur--by 3.10 +/- 3.34%. A significant 19.5% rise in bone alkaline phosphatase and a 16.5% fall in the level of CT were noted showing a stimulating effect of bivalos on bone formation and an inhibiting effect--on bone tissue resorption. Bivalos treatment raised quality of life of the patients: better motility, regress of depression, improved self-appraisal, decreased number of patients with pain in the spine, attenuated pain. The drug was well tolerated, unwanted effects arose in 15% patients, discontinuation of the drug because of toxicity occurred in 5%. Serious side effects were not observed. CONCLUSION: Strontium ranelate is effective in PMO and is well tolerated.

[New calcium-containing product for complex treatment of osteoporosis]. / Novyi kal'tsiisoderzhashchii pishchevoi produkt dlia kompleksnogo lecheniia osteoporoza.

The article presents results of clinical tests of calcium-containing product--dry breakfast "Bodrost"--having in its composition a mineral part of bones of slaughter animals, on patients with menopausal and senil forms of osteoporosis. A chemical composition of the developed product is presented. Results of biochemical tests of blood and urine as well as densitometry of bones of skeleton of patients at the age from 50 to 80 years old are presented. It is established that dry breakfast "Bodrost" can be recommended for complex treatment of osteoporosis.

[Tests of durability characteristics of osteosynthesis of femoral neck fractures by different fixators under static and dynamic loading]. / Ispytaniia prochnostnykh kharakteristik osteosinteza perelomov sheiki bedra raznymi fiksatorami pri staticheskikh i dinamicheskikh nagruzkakh.

Test bench experiments on the models of femoral neck bone fractures with the use of various kinds of latches has been carried out for evaluation of durability characteristics of the osteosynthesis, using universal test machine "Zwick-1464". 40 preparations of proximal-diaphysis parts of the femoral bone from 28 females and 12 males (mean age 71 years) were used one day after death. The models of basal, transcervical and subcapital fracture were formed with the angle between its planes and horizontal plane (the angle of Pauel's) 30, 40 and 70 degrees. The models of fractures underwent static and dynamic loads, the results being fixed automatically in graphics. The obtained data have confirmed the dependence of the stability of the osteosynthesis by tested fixators on the size of Pauels' angle: the more was this value the less was the firmness of the junction. Dependence of the firmness of fixation of bone fragments on location of the fracture in femoral neck was noted. The differences of durability characteristics of created constructions in basal, and transcervical fractures of types I and II by Pauels are insignificant. The authors think that the least invasive mode for fixation among tested constructions is osteosynthesis with V-shaped bunch of needles, which produced minimal trauma for bone tissue and created resilient tension in the system of bone fixator (latch), which is especially important in osteoporosis.

[Treatment of bone disorders in renal diseases]. / Lechenie patologii kostnoi sistemy pri zabolevaniiakh pochek.

AIM: To study possible correction of bone disorders (osteopenia, Ca/P-imbalance, bone pain, limited volume of indolent movements) which are still a serious complication associated with renal diseases and pathogenic therapy (steroids). MATERIALS AND METHODS: The bone disorders were treated in 10 uremic hemodialyzed patients (8 men, 2 women; group 1) with vitamin D3 (calcitriol made in Russia) + rhEPO (recormon; Boehringer Mannheim), in 15 patients (15 women, 0 men) with lupus-nephritis (group 2) with vitamin D3 (n = 5, group 2a) or miscalcic (Sandoz) (n = 10, group 2b), in 2 patients (2 men, 0 women) with glomerulonephritis (group 3) with vitamin D3 + miacalcic. Additionally all the patients received Ca salts. In groups 2 and 3 renal function was normal. The duration of the treatment was 3-6 months. RESULTS: In all the groups we obtained an analgetic effect (attenuation of bone pain and more indolent movements), improvement of life quality, diminished need in analgetics, elevation of serum Ca level (p > 0.05). CONCLUSION: Treatment of renal patients with bone affection with vitamin D3 and miacalcic has an analgetic effect, improves life quality.

[The efficacy of osteoquin in treating the postmenopausal and senile forms of osteoporosis]. / Effektivnost' osteokhina pri lechenii postmenopauzal 'noi i senil'noi formy osteoporoza.

A 1-year administration of osteoquine (7-isopropoxyisoflavon) to 20 patients with postmenopausal and senile systemic osteoporosis has shown a pronounced analgetic effect of this drug, its ability to stop the loss of and in some instances to increase bone mass, to stimulate osteogenesis.

[Osteopenic syndrome in liquidators of the aftereffects of the accident at the Chernobyl power plant]. / Osteopenicheskii sindrom u uchastnikov likvidatsii posledstvii avarii na Chernobyl'skoi atomnoi élektrostantsii.

Bone system was examined in 112 liquidators; in 71 of these osseous tissue density was studied by osseous densitometer using bienergetic x-ray absorptiometry and in 45 x-ray examinations, analyses of biochemical and hormonal parameters were carried out. Spinal painful syndrome was detected in 61 to 82% of the examinees. For analysis of densitometric and x-ray parameters the liquidators were divided into 2 groups: group 1 included those who worked at the power plant in 1986 (55%) and group 2 were those who worked there in 1987-1989. Radiation doses in group 1 reliably surpassed those in group 2 (p < 0.001). Bone mineral density in the lumbar vertebrae was significantly lower in group 1 as against group 2 and lower in both groups vs. controls. More than 5% osseous mineral loss was revealed in 73% of group 1 liquidators and in 43% of group 2 ones. Analysis of spinal roentgenograms in 45 liquidators showed a high incidence of negligible and moderately expressed osteoporosis without compression fractures of vertebral bodies: osteopenia signs were found in 87% of group 1 examinees complaining of pain in the spine and in 73% of group 2 examinees; signs of osteochondrosis and spondylosis were detected in 40% of group 1 and in 47% of group 2 subjects. Hence, a higher incidence of osteopenia in liquidators, more manifest condition and its higher detection rate in subjects exposed to higher radiation doses indicate a certain contribution of radiation factor to the development of the osteopenia syndrome in liquidators.

[Systemic osteoporosis in women]. / O sistemnom osteoporoze u zhenshchin.

This paper is based on investigation of biopsies from the upper flaring portion of the ilium of 53 women, sick of systemic osteoporosis. The results of quantitative evaluation of the osseous tissue parameters by means of histomorphometric method allowed to reveal systemic osteoporosis of 4 types, note distinctions between osseous tissue loss mechanisms in case of systemic osteoporosis and age atrophy of bones. Comparison of osseous tissue quantitative parameters with the peculiarities of microanatomy of trabeculae allowed to verify the degree of disturbance of such remodelling mechanisms as resorption and osteogenesis for each of 4 types. The possibility of fractures of axial skeleton and limb bones at normal value of spongy bone in biopsies from the upper flaring portion of the ilium has been demonstrated.

The state of human bone tissue during space flight.

The results of studying the bone tissue of cosmonauts after the flights (4-8 month) have been compared to the data of investigating the healthy individuals during head-down tilt (HDT, 370 days). Noninvasive methods (computer tomography, gammaphoton absorptiometry) revealed a decrease in the vertebral spongy mineral density or a increase of this parameter by a similar magnitude versus the individual preflight values in some cosmonauts. During studies of clinical cases of osteoporosis it was shown that the vertebral mineral density ratios and presence or absence of vertebral compression fractures in different age groups are nonequal.

[Pathogenetic aspects of studying clonal properties of bone marrow stromal cells in diseases of the osteoarticular system]. / Patogeneticheskie aspekty izucheniia klonal'nykh svoistv stromal'nykh kletok kostnogo mozga pri zabolevaniiakh kostno-sustavnogo apparata.

Properties of clonogenic stromal fibroblasts of bone marrow which are precursors of osteo- and chondrogenesis, of patients with different diseases of osteoarticular apparatus have been studied. Peculiarities of their reaction on growth-stimulating influence of nonstromal auto- and xenogeneic cells have been demonstrated. The possibilities of data application for studying of pathogenesis of hereditary osteochondrodysplasias as well as other groups of the skeleton affections are considered.

[The sex steroid content of the blood serum in women suffering from postmenopausal osteoporosis]. / Soderzhanie polovykh steroidov v syvorotke krovi zhenshchin, stradaiushchikh postmenopauzal'nym osteoporozom.

The levels of estradiol, estrone, androstendione, and testosterone were investigated in 25 women aged 56-69 with postmenopausal osteoporosis and in healthy women using radioimmunoassays. Relatively high levels of estradiol, estrone and androstendione were revealed in the study group as compared to the control group. The results obtained showed no association between the development of postmenopausal osteoporosis and deficiency of estrogens because in the healthy controls a decrease in the level of sex hormones was more noticeable. Taking into account the mechanism of the effect of estrogens on osseous tissue and its receptors, calcitonin secretion and, possibly, vitamin D3 synthesis, one can regard a relative elevation of the level of estrogens in postmenopausal osteoporosis as a compensatory protective phenomenon.

Effects of a bisphosphonate (1-hydroxy ethylidene-1,1 bisphosphonic acid) on osteoclast number during prolonged bed rest in healthy humans.

Acute osteoporosis is known to occur after immobilization in spinal cord injured patients and is related to an early increase in osteoclastic bone resorption. Whether osteoporosis develops in healthy immobilized human patients is still a matter of controversy. Furthermore, acute osteoporosis was thought to be a good model to study the effects of weightlessness on the human skeleton and to adapt preventive procedures. A bed rest experiment was developed in the USSR on 15 healthy human volunteers to determine the precise effects on bone structure and cell activities. A preventive protocol, including an anti-osteoclastic drug (1-hydroxyethylidene-1,1 bisphosphonic acid; K salt) was investigated. Two transiliac bone biopsies were performed on the 15 individuals before and at the end of the 120-day bed rest period. Undecalcified bone biopsies were studied with automatic and semi-automatic image analyzers specially devoted to bone histomorphometry. Trabecular bone volume, osteoid amount, and eroded surfaces were measured. Osteoclast number was measured after histochemical identification of tartrate-resistant acid phosphatase. After the bed rest period, an insignificant bone loss was observed in healthy humans while osteoclast number was highly increased. In bisphosphonate-treated subjects, osteoclast number was markedly reduced and so was osteoid amount. Bisphosphonates were shown to present a highly cytotoxic activity on osteoclasts, a finding that has never been demonstrated in normal subjects.

[Reaction of osseous tissue and the osteoclast population in rats to biphosphonates and vitamin D3 under conditions of hypokinesia]. / Reaktsiia kostnoi tkani i populiatsii osteoklastov krys na bisfosfonaty i vitamin D3 v usloviiakh gipokinezii.

Oral administration of hydroxy-dimethyl aminopropylene biphosphonate (DMAP) at a dose of 0.5 mg/kg increased the volume density (mass) of trabecular bone in the tibial metaphysis of untreated rats and helped to maintain it at the normal level in hypokinetic rats. Oral administration of hydroxy-ethylidene biphosphonate (OEDP) at a dose of 20 mg/kg and vitamin 24,25(OH)2D3 at a dose of 1,25 micrograms did not induce any quantitative changes in bones of untreated or immobilized rats. The combined treatment with either biphosphonate and vitamin D3 exerted a similar effect as compared to that of biphosphonates used singly. During hypokinesia the total amount of osteoclasts declined. This effect was also seen in response to biphosphonates and vitamin D3. The two biphosphonates produced an opposite effect on the osteoclast population in untreated animals: it increased in response to OEDP and decreased in response to DMAP. In contrast to OEDP, low doses of DMAP can efficiently inhibit bone resorption upon various routes of its administration and can be viewed as a preventive and therapeutic drug in the case of osteoporosis.