КОСТНЫЙ ОБМЕН И МИНЕРАЛЬНАЯ ПЛОТНОСТЬ КОСТНОЙ ТКАНИ ПОЯСНИЧНЫХ ПОЗВОНКОВ У ЖЕНЩИН С ПЕРВИЧНЫМ БИЛИАРНЫМ ЦИРРОЗОМ ДО И ПОСЛЕ ОРТОТОПИЧЕСКОЙ ТРАНСПЛАНТАЦИИ ПЕЧЕНИ

Aim. To elucidate the role of cholestasis and menopausal status in the development of osteoporosis in women with primary biliary cirrhosis (PBC) before and after orthotopic liver transplantation (OLT). Methods and re- sults. There were fulfilled 74 estimations of biochemical markers of bone metabolism, estrogen (E2), parathy- roid hormone (PTH) endogenous secretion so as mineral content of lumbar vertebras in 21 women with PBC (10 women before and 17 in different terms after OLT). Bone turnover disturbances were characterized by delay of bone formation associated with hyperbilirubinaemia before OLT while increased bone turnover following OLT. Bone resorption markers correlated inversely with E2 in postmenopausal women and positively with PTH in premenopausal women. Conclusion. Bone wastes degree depended on hard and duration of disease before OLT so as menopausal status after OLT. In postmenopausal women bone wastes were associated with degree of endogenous E2 decreasing, increased bone turnover, and graft dysfunction. Цель исследования: изучение роли холестаза и менопаузального статуса в развитии остеопороза у женщин с первичным билиарным циррозом (ПБЦ) до и после ортотопической трансплантации печени (ОТП). Методы и результаты. У 21 женщины с ПБЦ (у 10 до и у 17 в различные сроки после ОТП) исследовали в динамике (74 исследования) биохимические маркеры костного обмена, минеральную плотность кости поясничных по- звонков, а также эндогенную секрецию эстрадиола (Е2) и паратиреоидного гормона (ПТГ). Нарушения кост- ного обмена до ОТП характеризовались подавлением костного формирования, связанным с гипербилируби- немией, после ОТП – ускорением костного обмена. Маркеры костной резорбции коррелировали обратно с секрецией Е2 у женщин в постменопаузе и прямо с секрецией ПТГ у женщин в пременопаузе. Заключение. До ОТП выраженность костных потерь была связана с тяжестью и продолжительностью холестаза, а после ОТП, кроме того, и с менопаузальным статусом. Костные потери у женщин в постменопаузе зависели от степени снижения эндогенной секреции Е2, ускорения костного обмена и дисфункции трансплантата.

РАЗРАБОТКА МЕТОДА ОПРЕДЕЛЕНИЯ ГРАДИЕНТНОЙ И АКТИВНОЙ РЕАБСОРБЦИИ КАЛЬЦИЯ ДЛЯ ОЦЕНКИ ФУНКЦИИ ПЕРЕСАЖЕННОЙ ПОЧКИ

The dependence between minute calcium and sodium excretion from 1 L glomerular filtrate (CaE/GFR; NaE/GFR) with NaE/GFR from 0,1 to 9,71 mmol/l GFR was studied in 103 health volunteers. There was received asymptotique curve with r2 = 0,54; Y = 0,06 [1 – exp (–x/2,34)]. The nomogramm with confidence intervals of 95% was built. On the basis of renal physiology it was offered differentiate gradual (to electrochemical gradiate created by sodium reabsorbtion) and active calcium reabsorbtion. It was assumed that gradual calcium reabsorbtion is equel to sodium reabsorbtion and may be estimate by NaE/GFR, CNa/GFR. We considered that active calcium reabsorbtion is normal if the correlation between CaE/GFR and NaE/GFR is inside being decreased if the correlation is higher and increased if the correlation is lower probable intervals. We proposed T-score CaE/GFR as the quantative parameter of active calcium reabsorbtion. It varied in health volunteers from –1,74 to +2,15. The method was applied in 236 recipients of allotransplanted kidney. На материале исследования 103 здоровых добровольцев проанализировано соотношение между минут- ными экскрециями кальция и натрия из 1 л клубочкового фильтрата (CaE/GFR, NaE/GFR) при NaE/GFR от 0,1 до 9,71 ммоль/л. Установлено, что соотношение описывается асимптотической кривой с r2 = 0,54; Yx = 0,06 [1 – exp (–x/2,34)]. Построена номограмма с доверительными интервалами (95%). Исходя из физиологических данных о двух механизмах реабсорбции кальция – градиентном (ГР) по градиенту, со- здаваемому реабсорбцией натрия, и активном (АР), – предложено на основе номограммы анализировать их состояние: ГР – на основании величины NaE/GFR, а АР – на основании направленности и степени отклонений от кривой у здоровых. Предложено количественно оценивать состояние АР реабсорбции кальция на основании Т-критерия (у здоровых –1,75 – +2,15) . Проанализировано состояние ГР и АР у 236 реципиентов трансплантированной почки.

БИОХИМИЧЕСКИЕ МАРКЕРЫ РЕЗОРБЦИИ КОСТИ И ГОРМОНАЛЬНАЯ РЕГУЛЯЦИЯ КОСТНОГО МЕТАБОЛИЗМА ПОСЛЕ ПЕРЕСАДКИ ПЕЧЕНИ

Aim. Comparative evaluation of two biochemical markers of bone resorption and hormonal regulation of bone metabolism in liver recipients. Methods and results. Bоne densitometry of L2–L4 and neck of femur, serum level of some hormones (PTH, vitamin D3, estradiol, testosterone) regulating osteoclastogenesis as well as com- parative analyses of two bone resorption markers β-crosslaps and tartrate-resistant acid phosphatase type 5b (TRAP-5b) were fulfilled in patients after orthotopic liver transplantation (OLT). In 1 month after OLT bone density reduction of L2–L4 and neck of femur; decrease of vitamin D3, estradiol in women, testosterone in men and increase levels of bone resorption markers were observed. In 1 and 2 years after OLT the rise of bone density, increased levels of PTH, estradiol, testosterone and decreased β-crosslaps levels were revealed, while vitamin D3 and TRAP-5b levels remained stable. Conclusion. TRAP-5b was found to be a more speciffic marker of bone resorption, independent from collagen metabolism in liver. Osteoporosis defined in long-term period after OLT was associated with higher TRAP-5b and revialed in women with low estradiol level. Цель исследования: сравнительная оценка изменений двух маркеров резорбции и оценка состояния гор- мональной регуляции костной резорбции у реципиентов в различные сроки после трансплантации печени. Методы и результаты. В различные сроки после ортотопической трансплантации печени (ОТП) выпол- нено исследование минеральной плотности кости (МПК) в области поясничных позвонков (L2–L4) и шей- ки бедра, гормонов (ПТГ, витамина D3, эстрадиола, тестостерона), проведен сравнительный анализ двух маркеров резорбции БКЛ и КТРКФ-5б. Через 1 месяц после ОТП отмечено снижение МПК, уровня вита- мина D3, эстрадиола у женщин, тестостерона у мужчин, повышение маркеров резорбции кости. Через 1 и 2 года после ОТП минеральная плотность L2–L4 увеличивалась на фоне возрастания уровня ПТГ, половых гормонов и снижения БКЛ, в то время как уровни витамина D3 и КТРКФ-5б оставались стабильными. Заключение. Установлено, что КТРКФ-5б в ранние сроки после ОТП является более специфичным маркером резорбции кости. Остеопороз в поздние сроки ассоциировался с повышенными значениями КТРКФ-5б и у женщин с пониженным уровнем эстрадиола.

МИНЕРАЛЬНАЯ ПЛОТНОСТЬ КОСТИ ПОСЛЕ ПЕРЕСАДКИ ПЕЧЕНИ

Bone mineral density (BMD) was estimated twice in 18 recipents of ortotopic liver transplantation. There was decreased BMD in axial so as in peripheral skeleton in early time and in vertebral or hip Ward triangle in late time following transplantation being lower in primary biliary cirrosis then in cirrosis following chronic virus hepatitis despite tacrolimus immunosupression without prednisolon. Tacrolimus immunosupression with prednisolon in primary biliary cirrosis patients in late postoperative time was associated with hard BMD lowering which correlated with glucocorticoid therapy duration and prednisolon cumulative dosis. Минеральная плотность костной ткани (МПК) исследована повторно у 18 пациентов (36 наблюдений) после ортотопической трансплантации печени (ОТП). У реципиентов с первичным билиарным циррозом (ПБЦ) и с циррозом печени в исходе хронических вирусных гепатитов на фоне лечения такролимусом (без преднизолона) МПК в ранние сроки после ОТП снижена в области и осевого, и периферического скелета, притом у реципиентов с ПБЦ в достоверно большей степени, а в отдаленные сроки – только в поясничных позвонках или в треугольнике Варда. Иммуносупрессия такролимусом в комбинации с преднизолоном у реципиентов с ПБЦ в отдаленные сроки после ОТП ассоциируется со значительным снижением МПК во всех отделах скелета, выраженность которого определяется продолжительностью терапии преднизолоном и его кумулятивными дозами.

OSTEOPOROZ AKSIAL'NOGO SKELETA I EGO PRIChINY U ZhENShchIN V POSTMENOPAUZE V POZDNIE SROKI POSLE PERESADKI SOLIDNYKh ORGANOV (POChKI I PEChENI)

Purpose. The elucidation of the frequency and general determinants of postmenopausal women osteoporosis at the date >12 months following kidney allotransplantation (KA) and orthotopic liver transplantation (OLT). Materials and methods: There were fulfilled estimations of bone biochemical markers, estradiol, parathyroid hormone (PTH) in blood serum so as bone mineral density of lumbar vertebras (BMD) in 24 women following KA (32 estimations) and in 17 — after OLT (43 estimations). Results: Osteoporosis was revealed in 45% and 35%, hyperparathyroidism — in 90% and 37°% women after KA and OLT accordingly. BMD was positively correlated with free estradiol index in women after KA and OLT and inversely with PTH in women after KA so as with bone biochemical markers, disease duration before operation, level ofhyperbilirubinaemia in women after OLT and was more lower in women with cholestatic diseases. Conclusions: General determinants of osteoporosis in postmenopausal women following KA — estradiol deficit and hyperparathyroidism; after OLT — cholestatic liver diseases, transplant dysfunction and estradiol deficit. Osteoporosis in women with immunosupression without glucocorticoids and normobilirubinaemia so as type 1 postmenopausal osteoporosis associated with increased bone turnover and in women with transplant dysfunction — with increased bone resorption

BONE TURNOVER AND MINERAL DENSITY OF THE LUMBAR VERTEBRAE IN WOMEN WITH PRIMARY BILIARY CIRRHOSIS BEFORE AND AFTER ORTHOTOPIC LIVER TRANSPLANTATION

Aim. To elucidate the role of cholestasis and menopausal status in the development of osteoporosis in women with primary biliary cirrhosis (PBC) before and after orthotopic liver transplantation (OLT). Methods and re- sults. There were fulfilled 74 estimations of biochemical markers of bone metabolism, estrogen (E2), parathy- roid hormone (PTH) endogenous secretion so as mineral content of lumbar vertebras in 21 women with PBC (10 women before and 17 in different terms after OLT). Bone turnover disturbances were characterized by delay of bone formation associated with hyperbilirubinaemia before OLT while increased bone turnover following OLT. Bone resorption markers correlated inversely with E2 in postmenopausal women and positively with PTH in premenopausal women. Conclusion. Bone wastes degree depended on hard and duration of disease before OLT so as menopausal status after OLT. In postmenopausal women bone wastes were associated with degree of endogenous E2 decreasing, increased bone turnover, and graft dysfunction

ELABORATION OF METHOD FOR GRADIENT AND ACTIVE CALCIUM RENAL REABSORBTION DEFINITION FOR FUNCTIONAL ESTIMATION OF TRANSPLANTED KIDNEY

The dependence between minute calcium and sodium excretion from 1 L glomerular filtrate (CaE/GFR; NaE/GFR) with NaE/GFR from 0,1 to 9,71 mmol/l GFR was studied in 103 health volunteers. There was received asymptotique curve with r2 = 0,54; Y = 0,06 [1 – exp (–x/2,34)]. The nomogramm with confidence intervals of 95% was built. On the basis of renal physiology it was offered differentiate gradual (to electrochemical gradiate created by sodium reabsorbtion) and active calcium reabsorbtion. It was assumed that gradual calcium reabsorbtion is equel to sodium reabsorbtion and may be estimate by NaE/GFR, CNa/GFR. We considered that active calcium reabsorbtion is normal if the correlation between CaE/GFR and NaE/GFR is inside being decreased if the correlation is higher and increased if the correlation is lower probable intervals. We proposed T-score CaE/GFR as the quantative parameter of active calcium reabsorbtion. It varied in health volunteers from –1,74 to +2,15. The method was applied in 236 recipients of allotransplanted kidney

ROL' POLOVYKh GORMONOV V REGULYaTsII KOSTNOGO OBMENA i mineral'noy plotnostikostnoy tkani u muzhchin v pozdnie sroki posle allotransplantatsii trupnoy pochki

Lumbal spine and hip bone mineral density (BMD), bone turnover markers [bone alkaline phosphatase (bALP), osteocalcin (OC), aminoterminal procollagen I propeptide, bone acid phosphatase (bACP), ß-crosslaps (CTX)], sex hormones [testosterone, estradiol (E2), sex hormone-binding globulin (SHBG), free androgen index (FAI), free estrogen index (FEI)], parathyroid hormone (PTH), osteoprotegerin (OPG) and insulin-like growth factor-1 (IGF-1)] were determined in 39 men in age 42±10 years (33 with well renal function and 6 - with renal failure (RF) 44±26 months following KT receiving triple immunosuppressive therapy (CysA, prednisolone and azathioprine). Increased CTX, bACP, OC and decreased bALP so as BMD were associated in men following KT with low testosterone, SHBG and IGF-1 and high E2, OPG and PTH. There was more degree of bone turnover disturbances, decreased BMD, PTH hypersecretion and low FAI in RF. There were significant positive relationships between serum testosterone and E2, FEI and FAI, bALP and E2, bALP and FEI, femur BMD and FAI, femur BMD and FEI, OPG and E2, IGF-1 and PTH. There were significant inverse correlations between serum CTX and FAI, CTX and FEI, hip (spine) BMD and SHBG, hip (spine) BMD and PTH so as between PTH and FAI, PTH and FEI. So bone turnover disturbances, hip BMD losses and PTH hypersecretion in men at late time following KT associated with sex hormone deficiency. Predictor of high bone turnover and as vertebral as femur bone losses after KT besides PTH hypersecretion was serum SHBG. Decreased IGF-1 was the reason of bone forming suppression and possibly was following cyclosporine hepatotoxicity. OPG increasing was associated partly with high estradiol and was compensatory to attenuation of bone resorption and bone losses

BIOCHEMICAL BONE MARKERS AS PREDICTORS OF BONE LOSSES FOLLOWING LIVER TRANSPLANTATION

24 recipients after ortotopic liver transplantation (9 women and 5 men) 18–57 years aged were studied in 1–2 and then through 4–18 months following operation. Bone mineral density (BMD) in repeated estimation in 13 recipients was elevated on 14 ± 10,5% and in 11 recipients was decreased on 2,5 ± 2,56%. BMD elevation was associated with bone remodelling normalization. BMD lowering followed transplant dysfunction, glucocorticoid therapy, bone resorption increasing and bone formation suppression