JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol 9 - N°4 /2014
Khao sat n6ng do vitamin 25(OH)D3 trong huylt thanh d benh nhan viem cot s6ng dinh khop
Evaluating the Serum Vitamin 25{OH)D3 Level in Ankylosing Spondylitis
Nguyen Mai Hong Benh vien Bach Mai
Tom t i t
Muc tieu: 1. Khao sat ndng dp vitamin 25(OH)D3 huy^t thanh d bpnh nhan viem cpt sdng di'nh khdp.
2. Khao sat mdi lien quan gida ndng dp vitamin 25(OH)D3 huyet thanh va mUc dp nang cCia benh Viim cot sdng dinh khtip. Doi tugng va phuang phdp: nghien cilu m d t i c i t ngang, gdm 40 benh nhan VCSDK dupc cha'n doan theo tieu chuan New York sda ddi 1984, ed tudi s 17 tai benh vien Bach Mai tU thang 01/2013 den thang 01/2014, khdng bi benh rdi loan chuyen hda xuong, khdng bj benh gan, than, khdng dung cae thudc i n h hudng tdi chuyen hda vitamin D. Ket qud vd Icet ludn: 90% benh n h i n cd ndng do vitamin 25(OH)Dj huyet thanh thap han gia tri binh thudng; ndng dp vitamin 25(OH)D3 huyet thanh trung binh: 20,6±7,6ng/ml; Cd mdi lien quan gida ndng dp vitamin 25(OH)D3Vdi cac bieu hi^n lam sang ( mUe dp dau theo VAS, ehi so BASDAI) va can lam sang ( m a u i i n g , CRP).
TUkhda: Vigm cpt sdng dinh khdp, vitamin 25(OH)D3.
Summary:
Objective: 1. To evaluate serum vitamin 25(OH)D3 concentrations in the patients with ankylosing spondylitis. 2. To assess the relationship between 25(OH)D3 levels and disease levels. Subject and method: A cross-sectional study included 40 patients meeting the New York A l 984 criteria for ankylosing spondylitis, at the age of > 17 at Bach Mai Hospital from January 2013 t o January 2014. Result and conclusion: The mean serum vitamin 25(OH)D3 level was 20.6±7.6ng/ml; 90% of the patients had serum vitamin 25(OH)D3 concentrations below 30ng/ml. There was the relationship between vitamin 25(OH)D3 levels and pain levels, BASDAI, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP).
Keywords: serum vitamin 25(OH) D3: ankylosing spondylitis
I.Oatvande: thuyet ve nguyen nhin v i co che benh sinh cua
Viem cpt sdng dinh khdp (VCSDK) l i mdt benh ''^"^' " " j ' " ' ' ' 9'^,™3.h° « ehe' nhiem khuin tren viem khdp man tfnh. Benh thudng gap d nam gidi, " / ' " " ' ' "^l "T^ ! " ' ' ' " ' " ' " ' ' ' ^ ^ ' " '"" " ' t r i tudi. Ty le benh trong cdng ddng khoing 1/500 ''^^" ''"?. " " * " / ^ ! ' ^ ' ^'"^" ^"^ " ' ^ " ^ " '"^ * ™ 3'»
[11. VCSDK l i mdt trong nhdng benh ly co xuong ™\^y"*ines nhu TNF- a. Mdt so nghien cdu da chl khdp giy t i n phe' ning nd nhat cho ngudi benh v i '"}"^ * ^^"^^ " ' ' ' " "'^'^ " ^ ' ' ° " 9 " ' " ' ' '^'^''P " '•
l i ginh nang cho gia dinh v i xa hdi. Cd nhieu gii " " " ' """"^ f" ^ " " - ^''^'"'"' ° ™ ""' " * " " = " " ™ trong chuyen hda xuong. Ngoai ra, vitamin D cdn cii vai trd trong cic md khic ngoii xuang. SuthiSu hgt Phan bifn khoa hfic:. PGS.TS. LE THU HA vitamin D da duoc chdng minh cd lien quan den gis
t a n g n g u y co cua m d t s6 benh nhU benh ung t h i i , benh Dai t h a o d i l d n g t y p 2, benh t i m mach, benh truyen n h i e m , va dac biet la benh t i i mien...[4]. Co nhieu n g h i e n ciJu t r o n g thiic nghiem chu'ng t 6 vitamin 25(OH)D3 c6 vai t r o lic che mien djch t r o n g ca mien djch djch t h e va mien djch te bao [2].
Vitamin D3 [1,25(OH)2D3] va cac dan xuat cua vitamin D3 CO tac d u n g sinh hpc t h o n g qua receptor dac hieu cua v i t a m i n D 6 nhan te bao. Trong viem cot sdng d i n h kh6p sii thieu hut vitamin D duoc cho la yeu t o tien khdi phat benh va lam nang t h e m miic dp cua b e n h [5,6],
d Viet Nam chung toi chUa thay co nghien cu'u nao danh gia n o n g d p cua vitamin D d benh nhan viem cot song d i n h k h d p . Vi vay, chung t o i tien hanh nghien cu'u de tai: "Nghien ciiu x5c djnh n o n g d p , vitamin 25(OH)D3 d b e n h nhan viem cot sdng d i n h
khdp" v 6 i muc t i e u :
1. Xac d j n h n d n g d p vitamin 25(OH}D3 huyet I thanh d benh nhan VCSDK.
2. Moi lien q u a n giCfa n o n g do vitamin 2S(OH)D3 ( huyet t h a n h va mu'c d p nSng cua benh VCSDK.
2. Doi tiftfng va phUtfng phap nghien cuTu
2.1. Ddi tugng nghien cdu
Gdm 40 b e n h nhan viem c6t song d i n h khdp dieu tri tai khoa Co x u o n g khdp Benh vien Bach Mai gdm cd 38 BN nam va 2 BN nO, t h d i gian xd thang 01/2013 den t h a n g 01/2014 thda man cac tieu chuan chpn benh nhan dUdi day.
2.1.1. Tiiu chuan chgn binh nhdn
' Benh nhan dupc chan doan VCSDK theo tieu chuan New York 1984.
- Tudi > 17.
3. Ket quS va ban luan
3.1. Die diem chung cua nhom nghien cUu
B^ng 3 . 1 . Oac diem chung cua nhdm nghien cuTu - D d n g y t h a m gia nghien cdu.
2.1.2. Tieu chuan logi trd
• B^nh nhan bj benh rdi loai chuyen hda x u o n g . Benh nhan bj benh gan, than (men gan t a n g , phosphataze kiem tang)
- Hpi chdng kem hap t h u (viem rudt, benh Crohn).
SCf d u n g t h u o c anh h u d n g tdi chuyen hda vitamin D.
- Khdng d d n g y t h a m gia nghien cdu.
2.2. Phuang phip nghien edu
2.2.1. Thiet 1(6 nghiin cdu: p h i i o n g phap nghien ciiu m d t ^ c S t ngang.
2.2.2. Cdc bien s6 nghiin cdu: t h d n g tin t h u t h a p t h e o m^u benh an chung
- Thong tin chung; t u o i , gidi
- Lam sang: dp gian Idng ngtic; khocing each tay dat; dp gian cpt sdng that lung; mdc dp dau khdp (tinh t h e o t h a n g diem VAS); chi so BASDAI;
- C a n lam sang:
+ Xet n g h i e m danh gia t i n h trang viem (CRP, tdc dp mau Icing);
+ Xet nghiem ndng dp vitamin 25(OH)D3 huyet t h a n h : bSng xet n g h i e m mien djch dien hda phat quang. Ket qu5 danh gia nong dp vitamin 25(OH)D3 diia t h e o phan loai cua Holick 2007 [8].
+ X quang khdp c u n g chau 2.2.3. Xdly sdlieu
- Su" d u n g phan m e m t h d n g ke y hpc SPSS 16.0 - Dung t h u a t t o a n de t i n h gia trj t r u n g binh, t y le
%, so sanh cac t y le, cac t r u n g binh, sii khac biet cd y nghia t h o n g ke vdi m d c p < 0,01.
Thdng sd Tudi trung binh (nam)
Tudi trung binh khdi phat benh (nam) Thdi gian m i c bSnh trung binh (thing) D d gian CSTL (cm)
Nhdm nghien cdu X±SD
27,4±12,4 20,0±5,9 67,0±7,0 2,6±0,58
Min 15 13 1 2
iVlax 66 36 288
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JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol 9 - N°4 /2014
Thdng sd Khoing each tay dat (cm) VAS trung binh iVlau lang (mm) CRP (mg/dl) Tudi trung binh (nam)
Tudi trung binh khdi phat benh (nSm) Thdi gian m i c b^nh trung b"inh (thang) Op gian CSTL (cm)
Khoing each tay dat (em) VAS trung binh Mau lang (mm) CRP (mg/dl)
Nhdm nghien cdu X±SD
24,0+1,2 7,2±0,9 47,8+2,5 6,4±5,8 27,4±12,4
20,0±5,9 67,0±7,0 2,6±0,58 24,0±1,2 7,2±0,9 47,8±2,5 6,4±5,8
Min 0 5 15 1,8 15 13 1 2 0 5 15 1,8
Max 50
9 60 8,2 66 36 288 4 50 9 60 8,2
3,2. Oac diem nong dp vitamin 25(OH)D, huyet thanh d benh nhan VCSDK
3.2.1. Nong dd vitamin 25(0HjD, huyet thanh trung binh 6 binh nhdn VCSDK
Bing 3.2. Nong do vitamin 2S{0H)D, huyet thanh trung binh
Ndng dd vitamin25(OH)D3 (ng/ml) X ± S D 20,6 ± 7,6
Min 16,2
Max 32,5
Nhdn xit: Ndng dp vitamin 25(OH)Dj huyet thanh trung binh: 20,5 ± 7,6ng/ml, thap hon gia tri binh thudng.
3.2.2. Phdn logi nong dp vitamin 25(OH)D, huyet thanh
Bang 3.3. Phan loan ndng do vitamin 2S(0H)D, huyet thanh A tienh nhan viem cot sdng dinh khdp
Phan loai
lOng/ml n 2
%
5 10- 20ng/ml n 19
%
47,5 20- 30ng/ml n 15
%
37,5
>
30ng/ml n 4
%
10
Nhdn xet: cd 90% benh nhin cd ndng dp vitamin 25(OH)D3 huyet thanh thap hon gii trj binh thudng (30 ng/ml).
3.3. Moi lien quan giCta nong dp vitamin 25(OHID, huyet tbanh va miic dp nang cua 6en/i VCSDK
3.3.1. Moi llin quan giiia nong dd vitamin 25(0H)Di huyet thanh vd thiu chufng Idm sdng
3.3.1.1. Mdi lien quan giUa ndng dp vitamin 25(OH)D3 huyet thanh v i mdc dp dau theo thang diem VAS
Bing 3.4. Moi lien quan giCra ndng dp vitamin 25(OH)D, huyet thanh va miic do dau theo
thang diem VAS
Nhdm VAS>8 VAS<8 P
n 20 20
vitamin 25(OH)D3(ng/ml) 18,8±6,8 22,4±4,3
<0,05
Nhdn xit: Cd su khic biet ndng dp vitamin 25(OH)D3 huyet thanhd nhdm benh nhin cd chi so VAS a8 v i nhdm benh nhin cd chi sd VAS < 8 v*
p < 0,05.
3.3.1.2. Mdi lien quan gida ndng dd vitamin
25(OH)Dj huyet thanh va chl sd hoat ddng benh
(BASDAI).
TAP CHl Y DUQC L A M S A N G 108
B i n g 3.5. tAoi lien quan giCra ndng do vitamin 25{Oii)D3 huyet thanh va chi so hoat dong benh (BASDAI)
Nhdm BASDAI 27 BASDAI <7
P
n 31 9
Vitamin 25(OH)D3-ng/ml 19,8±7,1 23,4±7,9
<0,05
Nhdn xit: Cd su" khac biet ndng dp vitamin 25(OH)D3 6 nhdm benh nhan cd chi sd BASDAI > 7 va nhdm benh nhan co chi so BASDAI < 7 vdi p < 0,05.
3.3.2. Moi Iiin quan gida nong dd vitamin 25{OH)Dj vd cdc xet nghiim can idm sdng 3.3.2.1. Mdi lien quan gida nong dp vitamin 25(OH)D3 va chi sd mau lang
Bieu do 3.1. Moi lien quan gida nong do vitamin 25(OH)D3 va chi so mdu Idng
Nhdn xit: Cd m d i t d o n g quan tuyen t i n h nghich bien giOa nong d p vitamin 25(OH)D3 vdi chi sd mau I3ng (r= - 0,53; p <0,05).
3.3.2.2. Moi lien quan gida ndng dp vitamin 25(OH)D3 va chi so CRP
Bieu do 3.2. Moi lien quan gida nong dp vitamin ISiOHjD^ vd chi so CRP
Nhdn xit: Cd m o i t u o n g quan tuyen tfnh nghjch bien gida n o n g dp vitamin 25(OH)D3 vdi chi sd CRP (r = - 0 , 6 8 ; p < 0 , 0 5 ) .
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4. Ket luan
4.1. Die diim chung ddi tUpng nghien cUu
B d i t u p n g nghien cdu cd tudi khdi phat trung binh va tuoi t r u n g binh mac benh t u o n g ddi tr^.
Thdi gian bj benh trung binh keo dai. Mdc dp dau theo thang diem VAS t u o n g ddi cao.
4.2. Nong dp vitamin 25(OH)D3 huyet thanh trung binh & benh nhin viem egt song dinh khdp
Ndng dp vitamin 25(OH}D3 huyet thanh trung binh d benh nhan nghien cdu la 20,6±7,6ng/ml, thap hon g i ^ trj binh t h u d n g la 3 0 n g / m l . 90% benh nhan t r o n g nghien cdu ciia chung tdi cd ndng dp vitamin 25(OH)D3 huyet thanh thap < 30 n g / m l .
Vitamin D3 dc che cac te bao gai trudng thanh bai tiet cac cytokine nhU: IL-1, IL-6, TNF-a v^
interleukin-12 (IL-12), trong khi kich thich cac te bao gai bai tiet IL-10. IL-12 la mdt cytokine quan t r p n g t r o n g qua trinh hoat hda va hoat ddng cua te bao T h i . Vitamin D3 5nh hudng den tat c3 cac giai doan ph^t then cCia te bao gai, thuc day cac te bao gai chet theo chuong trinh. Ket q u ^ la dc c h ^ q u i trinh hoat hda cua cac te bao lympho T va lam giam su dap dng mien djch cua cac te bao lympho T. Vi vay vitamin D3 da dc che hoat ddng cua cac te bao lympho T thdng qua tac ddng true tiep len cac te bao gai.
Mat khac 6 benh nhan viem cpt sdng di'nh khdp cd s i i g i ^ m tiep xuc vdi anh sang mat trdi. Tang ndng dp TNF- a gay giam hoat d p n g cua enzyme 24- hydroxylase d than. Khiem khuyet cOa cac t h u t h e hap thu vitamin D d dudng rudt trong VCSDK.
43. Moi lien quan gida nong do vitamin 2S(OH}D3 huyet thanh vi mdc do nang cua lienh VCSDK
4.3.1. Moi iiin quan gida nong dp vitamin 25(OH)D^
vd mdc do dau theo thang diem VAS
Trong nghien cdu, chung tdi thay d nhdng b^nh nhan co chi so VAS £ 8 va nhdng benh nhan cd chi sd VAS < 8 CO sii khac biet ve ndng d p Vitamin 25(OH)D3 huyet thanh cd y nghia t h d n g ke. Thang diem VAS la thang diem danh gia cudng dp dau theo c5m giac chu quan cua benh nhan tai thdi diem nghien
cdu tren co sd lupng hda. Ket quS nay cung phu hc^ vdi cac nghien cdu trddc d d cua IVlermerci Baskan B va cs [7]: n o n g dp vitamin 25(OH)D3 t y 1^ nghich vdi mu'c d p dau theo t h a n g d i e m VAS.
4.3.2. Moi iiin quan gida nong do vitamin 25(OH}D3 vd chlso hoat dong binh BASDAI
BASDAI l i chi so d a n h gia miic d d hoat dong benh cCia benh nhan v i ^ m cot sdng d i n h khdp. Benh nhan tU danh gia trieu c h d n g cCia minh theo thang diem 10 t r o n g v d n g 1 t u a n trudc vdi 0: khdng c6 trieu chdng, 10: t r i m t r p n g , qua 6 cau hdi. Benh ho?t d p n g khi chi sd BASDAI a 4.
Trong nghien cdu, c h u n g tdi thay rSng d nhOng benh nhan cd chi sd hoat d p n g benh a7 va nhdng benh nhan cd chi sd hoat d p n g benh < 7 cd sii khac biet ve ndng d d vitamin 25(OH)D3 cd ^ nghTa thong ke. Cac nghien cdu trUdc d d cung chi ra rSng ndng dp vitamin 25(OH)D3 t>;' le nghjch v d i chi sd hoat d d n g benh BASDAI.
4.3.3. Moi llin quan gida nong dp vitan\in 25(OH)D3 vd xit nghiim ddnh gid tinh trgng viim
Trong nghien c d u nay, c h u n g t o i d u n g hai x^t nghiem: chi sd mau I3ng vci n o n g dp CRP de danh gia t i n h trang v i ^ m cCia b e n h nhan viem cpt sdng d i n h khdp. Ket q u i nghien cdu cho thay ndng 66 vitamin 25(OH)D31^ le nghjch vdi gia trj mau iSng vS ndng dp CRP. Ket q u i n g h i e n cdu nay tUOng t u nhi/
nghien cdu cCia Erten S va cs [4] va Lange U va cs [2].
5. Ket luan
Qua nghien cdu 40 BN VCSDK tai BV Bach Ivlai chung t d i thay:
5.1. Die diem nong do vitamin D huySt thanh dbinh nhin VCSDK
Ndng dp vitamin 25(OH)D3 huyet thanh trung binh l i : 20,6±7,6ng/ml. 9 0 % b e n h nhan cd ndng dp vitamin 25(OH)D3 huyet t h a n h t h a p < 30 n g / m l .
5.2, Moi lien quan gida nong do vitamin 25(OH)D3 huyet thanh vi mdc dd bieu bien benh
Cd sU khac biet gida n d n g d d v i t a m i n 25(OH)Dj vdi mdc d p dau t h e o t h a n g d i e m VAS va chi sd hoat d p n g b | n h .
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Ndng d p vitamin 25(OH)D3 t y le nghjch vdi chi so tdc d p m a u l^ng v i chf so CRP.
6. Kien nghj
Ty le t h i e u vitamin D d BN viem cot sdng di'nh khdp lien quan vdi t i e n trien benh, ve phac d d dieu trj song song vdi n h d n g t h u d c dieu tri co b i n cua benh can x e m xet bo x u n g vitamin D cung nhU thudc loang xuong t r o n g qua t r i n h dieu trj benh.
Tai lieu t h a m khcio
1 Tran Ngpc An (1980), "Benh viim cot song dinh khdp d mien Bac Viet Nam", l u i n an phd tien sy y khoa, trudng dai hpc Y H i Npi
2. Lange, U., et al. (2007), Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr, 85(6): p. 1586-91.
3. Durmus, B., et al. (2012) Does vitamin D affect disease severity in patients with ankylosing spondylitis? Chin Med J (Engl), 125(14): p. 2511-5.
Erten, S., et al. (2013) Decreased plasma vitamin D levels in patients with undifferentiated spondyioarthritis and ankylosing spondylitis. Intern Med, 52(3): p. 339-44.
Lange, U., et al. (2005) Association of 1.25 vitamin D3 deficiency, disease activity and iow bone mass In ankylosing spondylitis. Osteoporos Int, 16(12): p.
1999-2004.
Mai Thj Minh Tam (2008) Nghiin cdu mat do xUOng vd cdc yeu td lien quan trong benh viim cot song dinh khdp, Bai hpc Y H i Ndi.
Mermerci Baskan, B., et al.(2010) The relation between osteoporosis and vitamin D levels and disease activity In ankylosing spondylitis. Rheumatol Int, 30(3): p. 375-81.
Holick, M.F.(2008) Diabetes and vitamin D. Vitamin D Health.