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22-09-2012

Îñòàçà (êîñòíûé èçîôåðìåíò ùåëî÷íîé ôîñôàòàçû)

 

Ââåäåíèå

Êîñòíàÿ ôðàêöèÿ ùåëî÷íîé ôîñôàòàçû (îñòàçà) ñèíòåçèðóåòñÿ àêòèâíî äåëÿùèìèñÿ îñòåîáëàñòàìè. Äîêàçàíà êîððåëÿöèÿ ìåæäó óðîâíåì êîíöåíòðàöèè îñòàçû è ñêîðîñòüþ ôîðìèðîâàíèÿ êîñòè. Ýòè äàííûå ïîäòâåðæäàþòñÿ èíâàçèâíûìè ìåòîäàìè îáñëåäîâàíèÿ - ãèñòîìîðôîìåòðèåé è êèíåòèêîé ðàäèîàêòèâíîãî êàëüöèÿ â îðãàíèçìå. Êîñòíàÿ òêàíü äèíàìè÷íà, åå îáðàçîâàíèå è ðåçîðáöèÿ ïðîäîëæàþòñÿ âñþ æèçíü, ýòîò ïðîöåññ íàçûâàåòñÿ “ðåìîäåëèðîâàíèå”. Ðåìîäåëèðîâàíèå ÿâëÿåòñÿ ðåçóëüòàòîì ñëîæíûõ âçàèìîäåéñòâèé ìåæäó êîñòíûìè êëåòêàìè äâóõ òèïîâ: îñòåîáëàñòàìè, îòâåòñòâåííûìè çà îáðàçîâàíèå êîñòíîé òêàíè, è îñòåîêëàñòàìè, îòâåòñòâåííûìè çà åå ðåçîðáöèþ (1,2,3). Îáðàçîâàíèå è ðåçîðáöèÿ êîñòíîé òêàíè – íåçàâèñèìûå ïðîöåññû, êîòîðûå â íîðìå òåñíî ñîïðÿæåíû (2,4). Ýòà òåñíàÿ âçàèìîñâÿçü íåîáõîäèìà äëÿ ïîääåðæàíèÿ áèîõèìè÷åñêîé óñòîé÷èâîñòè ñêåëåòà, îáåñïå÷èâàþùåãî ñîõðàíåíèå îðãàíèçàöèè êîñòíîé ñòðóêòóðû, åå ðàçâèòèå è ïðî÷íîñòü (2,3,5). Ñ÷èòàåòñÿ, ÷òî êîíöåíòðàöèÿ êîñòíîé ùåëî÷íîé ôîñôàòàçû (îñòàçû) â ñûâîðîòêå êðîâè îòðàæàåò ñîñòîÿíèå ìåòàáîëèçìà îñòåîáëàñòîâ (6,7).

Äèàãíîñòè÷åñêîå çíà÷åíèå

Îöåíêà ñîñòîÿíèÿ ìåòàáîëèçìà êîñòíîé òêàíè íåîáõîäèìà äëÿ îïðåäåëåíèÿ òÿæåñòè îáìåííûõ çàáîëåâàíèé êîñòíîé òêàíè è ðåàêöèè íà òåðàïèþ. Ïîêàçàíî, ÷òî îïðåäåëåíèå êîíöåíòðàöèè îñòàçû â ñûâîðîòêå êðîâè öåëåñîîáðàçíî ïðîâîäèòü ïðè îáñëåäîâàíèè ïàöèåíòîâ ñ áîëåçíüþ Ïåäæåòà, îñòåîìàëÿöèåé, ïåðâè÷íûì ãèïåðïàðàòèðåîèäèçìîì, ïî÷å÷íîé îñòåîäèñòðîôèåé, îñòåîïîðîçîì è ìåòàñòàçàìè îïóõîëåé â êîñòè (6,7,8,9,10).

Îïðåäåëåíèå êîíöåíòðàöèè îáùåé ùåëî÷íîé ôîñôàòàçû ïðèíÿòî â êà÷åñòâå ìåòîäà äèàãíîñòèêè è êîíòðîëÿ ïàöèåíòîâ ñ áîëåçíüþ Ïåäæåòà. Êîñòíàÿ áîëåçíü Ïåäæåòà – ðàñïðîñòðàíåííîå çàáîëåâàíèå ñêåëåòà, ïðè êîòîðîì íàáëþäàåòñÿ ëîêàëüíàÿ ïðîëèôåðàöèÿ íîðìàëüíûõ êëåòî÷íûõ êîìïîíåíòîâ êîñòíîé òêàíè. Áîëåçíü Ïåäæåòà áîëåå ðàñïðîñòðàíåíà, ÷åì ïðåäïîëàãàëîñü ðàíåå, ñ ÷àñòîòîé â îáñëåäîâàííîé ïîïóëÿöèè 3–4% ó ïàöèåíòîâ ñðåäíåãî âîçðàñòà è 10–15% ó ïîæèëûõ (11). Ìîëîäûå ëþäè ýòîé áîëåçíè íå ïîäâåðæåíû. Ó áîëüøèíñòâà ïàöèåíòîâ áîëåçíü Ïåäæåòà ïðîòåêàåò áåññèìïòîìíî è îñòàåòñÿ íåðàñïîçíàííîé, ïîêà íå îáíàðóæàòñÿ ïàòîëîãè÷åñêèå èçìåíåíèÿ íà ðåíòãåíîãðàììå èëè â êîíöåíòðàöèè ùåëî÷íîé ôîñôàòàçû â ñûâîðîòêå êðîâè ïðè ìåäèöèíñêîì îáñëåäîâàíèè, ñâÿçàííîì ñ äðóãèìè ïðè÷èíàìè. ×àùå âñåãî ïàöèåíòû ñ ñèìïòîìàìè çàáîëåâàíèÿ æàëóþòñÿ íà áîëè è äåôîðìàöèþ êîñòåé.

Ðèñê îñòåîïîðîçà, äðóãîãî çàáîëåâàíèÿ ñâÿçàííîãî ñ ïðîöåññîì ðåìîäåëèðîâàíèÿ êîñòíîé òêàíè, îò÷àñòè çàâèñèò îò ðàçâèòèÿ ñêåëåòà è êîñòíîé ìàññû, à â ñòàðîñòè – îò âûðàæåííîñòè èñòîùåíèÿ êîñòíîé òêàíè. Ó çäîðîâûõ äåòåé ôîðìèðîâàíèå êîñòíîé òêàíè ïðåîáëàäàåò íàä ðåçîðáöèåé, ýòî îáóñëàâëèâàåò ðàçâèòèå êîñòíîé òêàíè è íîðìàëüíûé ðîñò ñêåëåòà (3). Ó çäîðîâûõ ñîâåðøåííîëåòíèõ ìîëîäûõ ëþäåé ôîðìèðîâàíèå è ðåçîðáöèÿ êîñòíîé òêàíè ñáàëàíñèðîâàíû, ïîýòîìó êîñòíàÿ ìàññà íå óâåëè÷èâàåòñÿ è íå óìåíüøàåòñÿ. Ñ âîçðàñòîì ó ìóæ÷èí è æåíùèí íà÷èíàåòñÿ äèñáàëàíñ ïðîöåññà ðåìîäåëèðîâàíèÿ êîñòíîé òêàíè, ïðè ýòîì ðåçîðáöèÿ íåçíà÷èòåëüíî ïðåâûøàåò ôîðìèðîâàíèå, ÷òî îáóñëàâëèâàåò ïðîäîëæèòåëüíîå ñíèæåíèå êîñòíîé ìàññû (1,2,4,12). Åñëè ýòîò äèñáàëàíñ ñîõðàíÿåòñÿ, ìàññà êîñòíîé òêàíè ìîæåò ñíèçèòüñÿ äî òîãî, ÷òî ñêåëåò áóäåò íåñïîñîáåí âûäåðæèâàòü îáû÷íûå íàãðóçêè è ñòàíåò ïàòîëîãè÷åñêè ïîäâåðæåí ïåðåëîìàì. ×ðåçìåðíîå ñíèæåíèå ìàññû êîñòíîé òêàíè ñ ïîâûøåíèåì ñêëîííîñòè ê ïåðåëîìàì èçâåñòíî êàê îñòåîïîðîç (5). Íàèáîëåå ÷àñòàÿ ôîðìà îñòåîïîðîçà ïðîÿâëÿåòñÿ ó æåíùèí â ïîñòìåíîïàóçå è ÿâëÿåòñÿ ðåçóëüòàòîì ñíèæåíèÿ âûðàáîòêè ýñòðîãåíîâ (2,12,13). Áûñòðîå ñíèæåíèå ìàññû êîñòíîé òêàíè ñîïðîâîæäàåòñÿ ñíèæåíèåì êîíöåíòðàöèè ýñòðîãåíîâ íà÷àëå ìåíîïàóçû èëè â ðåçóëüòàòå õèðóðãè÷åñêîãî óäàëåíèÿ ÿè÷íèêîâ. Áûñòðîå ñíèæåíèå ìàññû êîñòíîé òêàíè ÿâëÿåòñÿ ðåçóëüòàòîì ñîâìåñòíîãî äåéñòâèÿ äèñáàëàíñà ïðîöåññîâ êîñòíîãî ðåìîäåëèðîâàíèÿ è óñèëåíèÿ ìåòàáîëèçìà êîñòíîé òêàíè (5,14,15,16).  ÑØÀ îñòåîïîðîçîì ñòðàäàþò îêîëî 25 ìèëëèîíîâ æåíùèí â ïîñòìåíîïàóçå; îñòåîïîðîç ÿâëÿåòñÿ ïðè÷èíîé îêîëî 1,5 ìèëëèîíîâ ïåðåëîìîâ åæåãîäíî, âêëþ÷àÿ îêîëî 500 000 êîìïðåññèîííûõ ïåðåëîìîâ ïîçâîíî÷íèêà, 250 000 ïåðåëîìîâ áåäðà è 200 000 ïåðåëîìîâ äèñòàëüíîãî îòäåëà ëó÷åâîé êîñòè (2,5,17).

Çàìåñòèòåëüíàÿ ãîðìîíàëüíàÿ òåðàïèÿ – íàèáîëåå ÷àñòî íàçíà÷àåìûé âèä ëå÷åíèÿ äëÿ ïðåäîòâðàùåíèÿ ïåðåëîìîâ â ðåçóëüòàòå îñòåîïîðîçà ó æåíùèí â ïîñòìåíîïàóçå (4,5,18,19,20). Îäíàêî ìíîãèå æåíùèíû íå ìîãóò ïîëó÷àòü çàìåñòèòåëüíóþ ãîðìîíàëüíóþ òåðàïèþ èç-çà âîçìîæíîãî ïîâûøåíèÿ ðèñêà ðàêà èëè âîçîáíîâëåíèÿ ìåíñòðóàëüíûõ êðîâîòå÷åíèé. Ïîýòîìó, äëÿ ëå÷åíèÿ îñòåîïîðîçà ðàçðàáîòàíû äðóãèå ñîåäèíåíèÿ, òàêèå êàê áèñôîñôîíàòû, îáû÷íî èñïîëüçóåìûå ïðè ëå÷åíèè êîñòíîé áîëåçíè Ïåäæåòà, ñåëåêòèâíûå ìîäóëÿòîðû ýñòðîãåíîâûõ ðåöåïòîðîâ (ÑÌÝÐ) è êàëüöèòîíèí. Áëàãîäàðÿ àíòèðåçîðáòèâíûì ñâîéñòâàì áèñôîñôîíàòîâ, ÑÌÝÐ è êàëüöèòîíèíà ðåìîäåëèðîâàíèå êîñòíîé òêàíè ñíèæàåòñÿ, à, ñëåäîâàòåëüíî, óìåíüøàåòñÿ îáùàÿ ïîòåðÿ êîñòíîé ìàññû.

Îïðåäåëåíèå áèîõèìè÷åñêèõ ìàðêåðîâ ðåçîðáöèè êîñòè öåëåñîîáðàçíî ïðîâîäèòü ïðè ìîíèòîðèíãå îáìåííûõ çàáîëåâàíèé êîñòíîé òêàíè. Äëÿ êîíòðîëÿ ëå÷åíèÿ áîëåçíè Ïåäæåòà èñïîëüçóåòñÿ îïðåäåëåíèå äåçîêñèïèðèäèíîëèíà â ìî÷å, à òàêæå îáùåé ùåëî÷íîé ôîñôàòàçû â ñûâîðîòêå êðîâè. Îäíàêî îñòåîïîðîç ÿâëÿåòñÿ áîëåå òðóäíî ðàñïîçíàâàåìîé ðàçíîâèäíîñòüþ ðåìîäåëèðîâàíèÿ êîñòíîé òêàíè, è ïîýòîìó íåîáõîäèìû áîëåå ñïåöèôè÷íûå è ÷óâñòâèòåëüíûå ìàðêåðû.

Êîëè÷åñòâåííîå îïðåäåëåíèå in vitro êîñòíîé ùåëî÷íîé ôîñôàòàçû (îñòàçû) â ñûâîðîòêå èëè ïëàçìå êðîâè, ÿâëÿåòñÿ òåñòîì âûáîðà. Ïîêàçàíî, ÷òî îöåíêà èçìåíåíèé êîñòíîé ùåëî÷íîé ôîñôàòàçû öåëåñîîáðàçíà ó ïàöèåíòîâ, ïîëó÷àþùèõ òåðàïèþ ïî ïîâîäó îáìåííûõ çàáîëåâàíèé êîñòíîé òêàíè.

Ïîêàçàíèÿ ê íàçíà÷åíèþ èññëåäîâàíèÿ:

  • Äèàãíîñòèêà îáìåííûõ çàáîëåâàíèé êîñòè
  • Êîíòðîëü ýôôåêòèâíîñòè ëå÷åíèÿ îñòåîïîðîçà

Ïîâûøåíèå àêòèâíîñòè îñòàçû:

  • Ïàòîëîãèÿ êîñòíîé òêàíè (ñ ïîâûøåíèåì àêòèâíîñòè îñòåîáëàñòîâ èëè ðàñïàäîì êîñòíîé òêàíè): áîëåçíü Ïåäæåòà (äåôîðìèðóþùèé îñòåèò), îñòåîìàëÿöèÿ, áîëåçíü Ãîøå ñ ðåçîðáöèåé êîñòåé
  • Ãèïåðïàðàòèðåîç
  • Ðàõèò
  • Çàæèâëåíèå ïåðåëîìîâ
  • Îñòåîñàðêîìû è ìåòàñòàçû çëîêà÷åñòâåííûõ îïóõîëåé â êîñòè
  • Íàðóøåíèÿ ïèòàíèÿ (íåäîñòàòîê êàëüöèÿ è ôîñôàòîâ â ïèùå)
  • Ôèçèîëîãè÷åñêîå: ó íåäîíîøåííûõ, ó äåòåé â ïåðèîä áûñòðîãî ðîñòà, ó æåíùèí â ïîñëåäíåì òðèìåñòðå áåðåìåííîñòè è ïîñëå ìåíîïàóçû

Ñíèæåíèå àêòèâíîñòè îñòàçû:

  • Ãèïîòèðåîç
  • Íàñëåäñòâåííàÿ ãèïîôîñôàòàçåìèÿ (ðåöåññèâíîå àóòîñîìàëüíîå çàáîëåâàíèå, õàðàêòåðèçóþùååñÿ íàðóøåíèåì êàëüöèôèêàöèè êîñòè)
  • Íàðóøåíèÿ ðîñòà êîñòè (àõîíäðîïëàçèÿ, äåôèöèò àñêîðáèíîâîé êèñëîòû)
  • Íåäîñòàòîê öèíêà è ìàãíèÿ â ïèùå

Ïðè äèàãíîñòèêå ðåêîìåíäóåòñÿ îäíîâðåìåííîå îïðåäåëåíèå ùåëî÷íîé ôîñôàòàçû è îñòàçû.

Ëèòåðàòóðà.

1. Riggs L. Causes of age-related bone loss and fractures, Osteoporosis: Physiological Basis, Assessment, and Treatment. Deluca HF and Mazess R, eds., Elsevier (New York),1990, 7-16.

2. Status of Research in Osteoporosis. Osteoporosis Research, Education and Health Promotion. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health.

3. Canalis E. Regulation of bone remodeling, Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Favus MJ, ed., Raven Press (New York), 1993, 33-37.

4. Kleerekoper M and Avioli LV. Evaluation and treatment of postmenopausal osteoporosis, Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Favus MJ, ed., Raven Press (New York), 1993, 223-229.

5. Lindsay R. Osteoporosis. A Guide to Diagnosis, Prevention, and Treatment. Raven Press (New York), 1992, 1-39.

6. Epstein S. Serum and urinary markers of bone remodeling: assessment of bone turnover. Endocrine Reviews 9: 1998, 437-448.

7. Whyte MP. Alkaline phosphatase and the measurement of bone formation, Clinical Disorders of Bone and Mineral Metabolism. Potts JT and Frame B, eds., 1983, 120-125.

8. Garnero P and Delmas P. Assessment of the serum levels of bone alkaline phosphatase with a new immunoradiometric assay in patients with metabolic bone disease. J Clin Endocrin Metab 1993, 77: 1046-1053.

9. Cooper EH, Whelan P, and Purves D. Bone alkaline phosphatase and prostate-specific antigen in the monitoring of prostate cancer. The Prostate 1994, 25: 236-242.

10. Van Straalen JP, Sanders E, Prummel MF, and Sanders GTB. Bone alkaline phosphatase as indicator of bone formation. Clin Chim Acta 1991, 201: 27-33.

11. Merkow RL and Lane JM. Metabolic bone disease and Paget's disease in the elderly: II. Paget's Disease. Clin Rheum Dis 1986, 12: 70.

12. Lindsay R. Sex steroids in the pathogenesis and prevention of osteoporosis, Osteoporosis: Etiology, Diagnosis, and Management. Riggs L and Melton LJ, eds., Raven Press (New York),1988, 333-358.

13. Peck W. The pathogenesis of postmenopausal osteoporosis, Osteoporosis: Physiological Basis, Assessment and Treatment. Deluca HF and Mazess R, eds., Elsevier (New York), 1990, 3-6.

14. Christiansen C. Osteoporosis: Diagnosis and management today. Bone 1995, 17: 513S-516S.

15. Turner R, Riggs B and Spelsberg T. Skeletal effects of estrogen. Endocrine Reviews 1994, 15: 275-300.

16. Kanis J. Pathogenesis of osteoporosis and fracture, Osteoporosis. London: Blackwell Science Ltd.; 1994, 22-55.

17. Mack TM and Ross RK. A current perception of HRT risks and benefits, Osteoporosis: Physiological Basis, Assessment and Treatment. Deluca HF and Mazess R, eds., Elsevier (New York), 1990, 161-178.

18. Riggs L and Melton LJ. The prevention and treatment of osteoporosis. N Engl J Med 1992, 327: 620-627.

19. Guidelines for Preclinical and Clinical Evaluation of Agents Used in the Prevention or Treatment of Postmenopausal Osteoporosis. Division of Metabolism and Endocrine Drug Products, Food and Drug Administration. April, 1994.

20. Ribot C, Tremollieres F and Pouilles JM. Prevention of postmenopausal bone loss by long-term parenteral administration of 17B estradiol: comparison of percutaneous and transdermal route, Osteoporosis: Physiological Basis, Assessment and Treatment. Deluca HF and Mazess R, eds., Elsevier (New York), 1990, 137-145.