BAI HQl Hfl THAP KHflP HQC VlfT NAM UJN THgVII - Hfll NBHj KHOA HQC THttflNG NlgN LAN THgX
NGHliN Clill MARKER CHU CHUYEN XlAING OSTEOCALCIN VA BETACROSSLAP HUY^T THANH Of PHg Nff MAN KINH
D 8 Thj My Anh •• LS Thu Hi "•
VO Thj Thanh Hoa"
T 6 M TAT
Mpc tUu: Xdc d|nh ndng df Osteocalcin, Beta-Crasslap huySt thanh d phg nd mdn kinh vd mdi lien quan cua cdc marlter ndy vdl tuli, thdi gian mdn kinh vd mft df xutdng.
nuung phip nghUn cuV: TiSn cCru md td cdt ngang. Odi tupng nghiin ciiU 139 phg nu* chia thdnh 2 nhdm: nhdm nghlSn cuU 101 phg nO* man kinh (PNMK) tu nhlSn vd nhdm chijfng 38 phg nif trd tuoi tir 20-35 tgol, khde manh. Do mft df xg'dng bdng phu'dng phdp DEXA. Djnh Igtjng Osteocabn ((X) vd beta-crasslap (BQ hgyd thanh lOc ddi dieo nguyen ly "sandwlsh".
KSt qui: Tuoi trung binh nhdm PNMK 61,6±8,5tudi. Tgdl man kinh trgng binh 49,5±2,9tgol. PNMK loang xg'dng cd nSng df OC huyfi thanh 18,02±7,09 ng/ml vd BC huySt thanh 0,64±0,30 ng/ml, cao hdn cd y nghia thdng ke so vdi PNMK khong LX, p<0,05.' NSng df OC va BC ti If nghkh vdl mft df xuting cd xuting dCil, tuy nhien mgt df tgtAig qgan thap ( t g t ^ utig Id r = - 0,26 vd r = -0,28). Khdng thay khde bift ndng df OC, BC hgyet thanh glQIa nhdm phg nO' tre tool vd PNMK khdng LX; Chu^ thay sg' khde bift v€ ndng df OC, BC hgydt thanh theo tu6l vd thSl gian mdn kinh.
KSt lufn: Ndng df OsCeocakin vd Beta- Qosslap tdng cao d phg iv3 man kinh bang x g t ^ vd ndng df ndy ti If nghjch vdl mft df xutAig od xgtfngdul.
Tu" khoi: Loang xutdng, phit ni? man kinh, marker chu chuyen xiMig.
SUIMMARY
LEVEL OF OSTEOCALaN AND BETACROSSLAP SERUM IN POSTMENOPAUSAL WOMEN Objective: To assess level of Osteocakin, Beta-Crosslap serum and correlation between the biochemical serum v^lth age, menopausal time, BMD In postmenopausal women.
Subject and method; Cross-sectional descriptive. 139 women were distributed: patient group Include 101 postmenopausal women and the control 38 young healthy women wtw are 20- 35 years old. All vramen were examined BMD by DEXA and Investigated OC vd BC semm based on
"sandwish" theory.
Results: Mean age of postmenopausal women 61,6 ± 8,5 years okl. Rate of ohesity In patient group 31,7%. Mean menopausal age of postmenopausal women 49,5 ± 2,9 years oW. In postmenopausal osteoporotic women OC serum 18,02 ± 7,09ng/ml and BC semm 0,64 ± 0,30ng/ml are higher in postmenopausal women who dont have osteoporosis, slgnifkantiy, p<0,05. There are vreak contrary conelaUon between OC va BC serum wUi BMD of femoral neck (respectively r = - 0,26 and r = -0,28). No difference of OC, BC concentration between ttie young group and the postmenopausal women who dkint have osteopon»ls. No evidence of change OC and BC serum with age and menopausal duration.
Conclusions: level of OC vd BC semm Increase in postmenopausal osteoporotic women and the conoenbations contrary ooRElation wHi
* Hoc vien Quan y; ** Benh vien TW Quan dgi 108
Y H p c V l f T NAM T H A N G 9 - s 6 2/2012
BMD of femoral neck.
Keywords: Osteoporosis, postmenopausal women, biochemical bone marker.
I. D$T V X N OE
Lodng xuong (LX) vdi nhthig hfu qud ndng n^ md bfnh gdy ra d6i vdi siic Idhde cfng d6ng dd duoc TCYTTG dua vdo nhdm lifnh cd nguy co cao vk y tk vd xd hfi nhu bfnh dfng mach vdnh, ung thu vd dft quj.
Nhieu ngliien ciru dd cho thSy d phg nil mdn kmh (PNMK) do lugng estrogen gidm dd ldm gia tdng hdy xuong nhif u hon t$o xuong din tdi LX. Khodng 20% phg nO trdn 60 tudi cd LX. Khoi l u ^ g xuong dugic do ludng bdng mft df Idiodng cila xuong, cdn chuyin hda sinh hgc cua xuong dugc ddnh gid gidn tiep qua cdc marlcer chu chuyen xuong... Cdc marker chu chuyen xuong gdm marker tgo xuong nhu Osteocalcin, Phosphatase kidm dfc hieu cua xuong... vd marker huy xuong nhu Hydroxyprolin (HYP), cdc lien ket cdt ngang vdi telopeptide cda collagen type 1- N vd C... Nong df cdc marker chu chuyen xuong ludn bien ddi sdm hon so vdi mft df xuong do vfy thudng duoc su dung tren ldm sang trong tien lugng tinh trang mdt xuong, gdy xucmg vd theo ddi hifu qua dieu trj LX.
CJ Vift Nam, theo mft nghien cdu (2008) cd 100.000 ca gdy xuong d ntt vd 60.000 ca d nam, du kidn sS tdng Idn gap 2 ik tiong vdng 20 ndm tdi [trich ttr 3]. Nhdm ldm rd them nhihig thay doi ve chu chuyen xuong d PNMK chdng tdi tiln hanh:
"Nghien cilu marker chu chuyen xucmg Osteocalcin vd Beta-Crosslap d phy nil mdn kinh" nhdm mpc tidu:
1. Xdc dinh ning dg Osteocalcin, Beta- Crosslap huyit thanh dphv nii mdn kinh.
, 2. Nhfn xet mii lien quan gllra ndng df
Osteocalcin, Beta-Crosslap huyet thanh vdi tudi, thai gian man kinh vd mdt df xuong.
n. 0 6 l TU9N6 vi. PHl/ONG PHAP N G H I I N COU
2.1. Bii tufmg nghiin ciiu: 139 phg nil bao gfm:
Nhdm bfnh: 101 phy ntt mdn kinh (MK) tu nhien, mat kinh hodn todn tirong it nhat 12 thdng, tinh nguyfn tham gia nghien ciiu. Loai khdi nghidn ciiu nhttng BN: MK bdt bufc, mdc bfnh nfi khoa vd/ hodc ddng thu6c dnh hudng tdi MDX, dang dik trj LX, khdng hgp tdc nghidn cilu du.
- Nhdm chiing: 38 php nft trd tudi td 20- 35, khde manh. Loai khdi nghien ciiu nhiing phg nft dang cd thai hofc nudi con bi.
Cdc d6i tugng nghidn cihi dugc thdm ididm theo mau bfnh dn thong nhdt
2.2. Phinmg phdp nghiin ciru: Tien ciiu, md ta cdt ngang
2.3. Cdc tilu chuan vd qui trinh xit nghifm sir dgng trong nghiin cUu
- Do MDX bdng DEXA tai CSTL vd CXD trdn mdy Explorer hdng Hologic - M5'
- Tieu chudn chdn dodn loang xucmg theo WHO -1994
- Djnh lugng Osteocalcin vd Beta-ciosslap huydt thanh liic ddi theo nguyen ly "sandwish"
mdy Elecsys 2010-hang Roche tgi khoa Sinh hda-BfnhvifnTU'QD 108.
- Cdch xdc dinh mile cda marker chu chuyen xuong: Djnh lugng OC, BC huydt thanh d nhdm PN tre tu6i, xdc djnh X vd SD, lay dilm cdt gidi han dudi X -SD vd dilm cdt gidi han tirdn X +SD xdc dinh mile n^ng df cdc marker.
2.4.Xdr If si lifu. Bdng phuong phdp thong ke y hgc trdn phan mIm Epi info 6.04.
W Hpl HQl THfP KHflP Hgc VI$T NAM UN THgVII - Hfl NGHj KHOA HgC THi/dNG NlSN U N THtfX
III. KiT QuA NGHIEN cCru
3.1. Bfc diim chung cda nhdm nghiin cii'u.
Ofc diSm Tudi (ndm) Chieu cao (cm) Cdn ndnq (kq) BMI (kqlm') Tudi mdn kinh (ndm) Mft do
xutJnq
CSTL (q/cm') a D (g/cm') Tinh tr?ng LX
Thdi gian man kinh Bfnh kem tiieo
Loanq xul^nq Thu:a xutJnq Binh thudnq
< 5 ndm 5-15 ndm
>15 ndm Thoai hda khdp Khac (THA, OTO..)
Nhdm MK(n=101) X- SD 61,6 ± 8,5 154,0 ± 5,4 52,8 ±6,0 22,3 ± 2.4 49,5 ± 2,9 0,751 ± 0,163 0, 726 ± 0, 155
Ti Id % 59,4 (60/lOlBN) 29,7 (30/lOlBN) 20,8 (21/lOlBN) 28,7 (29/lOlBN) 38,6 (39/lOlBN) 32,7 (33/lOlBN) 34,7 (35/1018N) 19,8 (20/lOlBN)
Nhim trd tutfi (n=38) X- SD 27,0 ± 3,6 154,6 ± 3,5 49,9 ± 3,5 20,8 ± 1,1 0,889 ± 0,152 0,865 ± 0,108
3.2. Ning df Osteocalcin vd Beta-crosslap huyit Ihanh dphg nit min kinh Bdng 2. Ndng df marker chu chuyin xucmg
Ndng df marker huyetthanh (A'±SD)(nq/ml)
Osteocalcin Beta-Crosslap
Nhdm MK C6LX<"
(n = 71) 18,02 ± 7,09 0,64 ± 0,30
Khdng LX"' (n = 30)
12,17 ± 2,94 0,30 ± 0,18
Nhdm tr4tu«l<»
(n=38) 13,30 ± 5,30 0,29 ± 0,17
P
p('«<0,05p'"'
< 0,05. o'"' > 0.05 p'"'<0,05p"^
< 0,05. 0™ > 0,05 Nhfn xit: Nong df OC va BC huyet thanh d nhdm PNMK LX cao hon ro rft so vdi nhdm PNMK khdng LX, p < 0,05.
Bing 3. Phdn miic marker chu chuyin xuong d phy ntt mdn kinh OC thip < 8,0ng/ml va OC cao > 18,6ng/ml.
BC thip < 0,12ns/ml vd BC: cao > 0,46 ng/ml.
Miicdf PhSn miic 1 Thap
C6LX n = 7 1
6
%
8,4
Kh6ngLX nsSO
5
%
16,7 P
>0,05
Y HQC VI$T NAM THANG 9 - s6 2/2012 OC
Phdn mlj'c BC
Trunq binh Cao Thap Trunq binh Cao
35 30 1 22 48
49,3 42,3 1,4 31,0 67,6
25 0 3 23 4
83,3 10,0 76,7 13,30
<0,05
<0,05 •
<0,05
>0,05 Nhfn xet: ti if PNMK LX cd BC vd OC huydt thanh d muc cao nhilu hon so vdi nhdm khdng LX, tuy nhidn su khde bift cd y nghia chi thay d marker OC.
3.3. Mil liln quan giiia marker chu chuyin xuong vdi mft df xurong va mft so yiu li liin quan vdi loang xuong
Bing 4. Ndng dg cdc marker chu chuyin xuong theo tudi Tuoi
<55'"
(n = 19) 55-65<«
(n = 47) 65-750' (n = 20)
> 7 5 « (n=15)
Ndnq dd marker hu Osteocalcin (n=1011 Trung
vi 9,85 14,14 15,61 14,02
Min 0,78 4,08 5,07 4,36
Max 37,82 47,73 28,72 24,69
P p"<0,05 p"<0,05 p"<0,C5 p'^>0,05
vet thanh (nq/ml) Beta-Crosslap (n=101) Trung v|
0,39 0,60 0,56 0,57
Min 0,10 0,12 0,11 0,10
Max 1,05 1,66 1,34 0,78
P p"<0,05 p"<0,05 p"'<0,05 p^>0,05
Nhgn xet: Co sir khac biet ve n6ng dp cua marker chu chuygn xuofng a nhom MK < 55 tuoi so voi cac nhom tuoi > 55 voi p<0,05.
Bang 5, Nong df cac marker chu chuyin xucmg vd thdi gian Thdi gian
man kinh
<5ndm (n=29) 10- 15ndm(n=39)
>15 iiSm(n=33)
man kinh Ndng dd marker huyet thanh (nq/ml) Osteocalcin fn=:101)
Trung vi 15,72 15,90 14.02
Min 0,78 4,52 4,36
Max 37,82 47,73 28,72
P
>0,05
Beta-Crosslap (n=101) Trung vj
0.44 0,61 0,56
Min 0,10 0,19 0,07
Max 1,05 1,66 1,34
P
>0,05
Nhfn xet: Khdng thdy khde biet gitta ndng dg OC, BC vd thdi gian man kmh.
Bdl HOl HOI THft> KHflP HflC VlfT NAM LAN THUVII - HOl NGHI KHOA HflC THt/flNG NIEN U N THOX
Hlnhl. Tuong quan gitta nf ng df OC vd mft df xuong tai CXD d phy nO mdn kinh Nhfn xit: Cd m6i tuong quan mute ylu gitta MDX tai CXD vd ning df OC (r=
0,26).Khdng cd mfi tuong quan gitta MDX tai CSTL vdi ning df OC (r=- 0,1).
IV. BAN LUAN
4.1. Bfc diim chung
Nghien ciiu tiln hdnh ti-en 101 phy nft mdn kinh (PNMK) vd 38 phy ntt trd tuoi khde mfuih. Nhdm PNMK cd tuli tiimg binh 61,6 ± 8,5 hidi.... Tuli mdn kinh tnmg binh trong nghien cHu cda chiing tdi Id 49,5 ± 2,9 tuoi. Phin ddng phy ntt cd thdi gian mdn kinh > 5 ndm, ty If dudi 5 ndm id 28,7%. Dii vdi MDX d PNMK kit qud oho thiy MDX tai CSTL Id 0,751 ± 0,163g/cm^ CXD 0,726
± 0,155g/cm^ dlu thip hon cd ^ nghia so vdi nhdm phy ntt trd. Cd 59,4% PNMK cd lodng xuong CSTL vd 14,9% lodng xuong CXD.
Kit qud ndy ciing phi hgp vdi cdc tdc gid Gamero.P [7]; Ld Thu Hd (2007) [2]
4.2. Ning ttf Osteocalcin vi beta- crosslap huyit thanh &phg ntt mdn kinh.
Do chira cd gid trj tham chilu ning df binh thudng cua marker Osteocalcin (OC) vd Beta-Crosslap (BC)huylt thanh d ngudi Vift Nam nen chiing tdi dd khdo sdt tren 38 phy ntt tti khde manh td 20-35 tuoi. Ket qud Id
ning df OC huyet thanh tnmg bhih 13,30±5,30 ng/ml, BC huyit thanh trung bhih 0,29±0,17 ng/ml. Kit qud ndy ciing phi hgp vdi cdc tdc gid Iraj Nabipour (2008, ban) khdo sdt d nhdm phy nft t i 20-30 tuli flily nong df OC trung binh 12,44ng/ml vd BC tiimg binh 0,31ng/nil [8]. Weinbrenner.T (2003, Die) nghidn cuu 51 phy nft khde m?nh cd mii trung binh 25,5 ± 0,9 tali, cOng thiy ning df OC vd BC lin lugt Id 13,59 ± 1,09 ng/ml vd 0,238 ± 0,170 ng/ml [11].
Marker (X) dugc ting hgp trong xuong bdi cdc nguyen bdo xuong, Id mft protein collage khdng Idn vd dfc trung nhit tixmg xuong ngudi tnrdng thdnh. Uu dilm cia OC Id tinh dfc trung vd on djnh d timg cd thi. 6 PNMK cd lodng xuong, thilu canxi, phospho cd the din din ldm gidm Mnh thdnh cdc tinh the hydroxypatite vd gidm t^io xuong, tdng chu chuyin xucmg. Khi dd OC ty do Iuu hdnh trong mdu sd tdng Idn. Dilu ndy gidi thfch d PNMK cd LX ning df OC huyit thanh tdng cao. Pino vd cs [9] nghien ciu thiy OC Id mft
Y HOC VI$T NAM T H A N G 9 - S d 2/2012
marker chu chuyin xuong rit cd y ngMa trong chin dodn vd theo doi dilu trj LX cd chu chuyin xirong cao. Trong nghien cdu cua chiing tdi nhdm PNMK LX cd ning df OC tning btah 18,02 ± 7,09 ng/ml vd BC trung binh 0,64 ± 0,30 ng/ml. Gid tii ndy cao hon hdn vdi nhdm PNMK khdng lodng xucmg (p <
0,05). Khao sdt sy ho^t dfng cua cdc tl bdo t^o xuong thdng qua OC cung cho kit qud bdo cdo tuong ty d cdc nghidn ciu cua Cabrera [5].
Neu xdt vl phdn mic cua 2 marker chu chuyin xuong OC vd BC thi nhdm MK cd LX cd tdi 42,3% BN cd ning df OC tdng vd 67,6% BN c6 ning df BC tdng tirong khi d nhdm MK khdng LX khdng cd BN ndo cd ning df OC ting cao vd chl 13,3% cd ning dg BC tdng cao. Dilu ndy cimg phi hgp vdi nhfn dinh cua cdc nghidn ciu Id ndng df marker chu chuyin xirong cd xu hudng tdng cao d nhdm cd LX, ddng nghia vdi cd tdng chu chuyen xuong vd gidm sic manh cia xuong.
4.3. Mii liln quan gidra ning df Osteocalcin, beta-crosslap huyit thanh vdi mft df xuttng vi mft so yiu li lien quan vdi loang xinmg dphg ndrman kinh.
Lien quan giUa marker chu chuyin xuang vd mgt df xucmg.
Khdo sdt mii lien quan giiia marker chu chuyin xuong vd mft df xucmg ching tdi thiy cd mdi tucmg quan nghich mic df yeu gitta nong df cia cd 2 marker OC vd BC vdi mft dd xuong tai CXD (r = -0,26 vd -0,28).
Melton vd cs (1997) khi nghien ciu sy ttrong quan gitta ning df cac marker chu chuyen xuong vd mft df xuong cho thiy ndng df cdc marker chu chuyin xuong t^ If nghich vdi mat do xuong, tuy nhien hf so Wong quan thip [trich t i 7]. Nhfn dinh ndy cung tuong ty d cdc nghien ciu cia Gamero. P (2001) [7] vd Ravn. P (2002) [frich t i 8].
Patrick Gamero (1999) nghien ciu 305
PNMK thiy ning df cdc marker chu chuyin xuong cao cd lien quan din t^ If mit xuong sau 4 ndm [trich t i 7]. Gamero. P vd cs (2001) nghidn ciu 268 PNMK theo ddi tiong 4 ndm thiy ning df OC vd BC huyit thanh cd xu hudng tdng tuong ing Id •H,2%/ndm, p=0,003 vd +0,13W ndm, p = 0,70) [7]. Christiansen vd cs (1987) [6] da thiy cdc marker phosphatase kilm ddc hifu cho xuong, OC huyit thanh vd canxi, hydroprolin vd DPD nifu cd thi tidn lugng 60-70% tinh ti-ang mit xuong d PNMK.
Tuy nhien, mft si nghien ciu khde lai thiy cdc marker NTX, OC vd PTH chi gidi fliich dugc 43% sy bien doi ve tinh tiang mat xuong gitta cdc cd the.
Liln quan giUa marker chu chuyen xuang vd tuii.
Trong nghidn ciu cia ching tdi, ning df cdc marker chu chuyen xucmg gia tdng theo tudi, ndng df ndy thdp nhit d nhdm phy ntt dudi 55 tali, d cdc df tadi > 55 cdc gid tri trung vi cia ndng do cdc marker nay dlu cao hem cd y nghia thing kd so vdi nhdm
<55 tali, sy khac bift ndy la cd y nghla thing ke vdi p< 0,05. Tmh ti-ang tdng cao cua cdc marker OC vd BC huyet thanh d cdc nhdm PNMK LX d cdc dd tali > 55 tali cung phi hgp vdi tmh trang gidm mft df xuong tdng len d cac BN nay. Ket qud cia ching tdi phi hgp vdi nghien ciu cia Pino JD vd cs [9], nong dp OC, BC huyet thanh tang tiieo tali, sy khde bift cd y nghia tiling kd vdi p<0,05. cdc tdc gid ndy cdn thiy fixing 2 ndm diu tien cia MK chua fliiy cd sy khac bift ndng df cac marker ndy d phy ntt tiln man kinh vd PNMK.
Liln quan giUa marker chu chuyin xuang vd thdi gian man Unh.
Cdc nghien ciu cho fliiy cdc marker chu chuyin xucmg d cdc phy ntt man kinh fliudng tdng cao nhit d giai doan 5 ndm dau sau man kinh. a giai doan ndy do cd tdng tic df ludn
B»l Hfll HOl THAP KHflP HQC VI$T NAM U N THCTVII - Hfll NGH| KHOA HIJC THUONG NlEN L A N T W O X
hodn c i a xuong, qud trinh h i y xuong nhanh hon tao xucmg ldm k h i i lugng xuong gidm di vd n i n g df OC tdng mgt cdch cd y nghla.
Sau 8-10 ndm mdn kinh chu chuyin xucmg chfm lai vd n i n g df OC trd v l m i c c i a thdi ky tiln mdn kinh. Gamero.P (2001), khdo sdt BC huyit Uianh d PNMK thiy cd thi cdn cao din 40 ndm sau mdn kinh [7]. Trong nghidn c i u c i a ching tdi khdng tim tiiiy sy khde bift gitta ning dp cdc marker chu chuyin xuong vd tiidi gian mdn kinh (p>0,05), nguydn nhdn cd till do s i lugng BN trong cdc nhdm nghidn c i u c i a chung tdi cdn it.
V. KI'T LUAN
Nghidn c i u 101 phy ntt mdn kinh dilu tii tai khoa Ngi Thfn Khdp - B V T L T Q D 108 vd 38 phy ntt trd khde m ^ , c h i n g tdi r i t ra mft s i ket lufn sau;
- Nhdm phy ntt mdn kinh cd lodng xuong ndng df Osteocalcin huyit thanh Id 18,02 ± 7,09ng/ml; N i n g df Beta-crosslap huyit thanh: 0,64 ± 0,30ng/ml, cao hon cd y nghia tiling ke so vdi phy nft ti^ tali vd PNMK khdng LX vdi p < 0,05.
Khdng thiy cd sy khde bift v l n i n g df Osteocalcin, Beta-Crosslap huyit thanh gitta nhdm phy ntt trd t u l i vd PNMK nhung khdng LX.
- Ndng df Osteocalcm vd Beta-Crosslap huyit tfianh fl If nghich vdi mft df xuong cd xuong dii, tay nhidn m i c df tuong quan tfiip (r = -0,26 v d r =-0,28).
Chua tiiiy cd s u khde bift ve n i n g df Osteocalcin, Beta-Crosslap huyit thanh theo tali vd thdi gian mdn kinh.
TAI LlfU THAM KHAO
1. Lc Thu Hd (2007). "NghiSn cihl tinh trjlng lodng xuong d 175 phu nil bdng phuong phdp DEXA tai Bfnh vifn Tmng LTong Qudn Ddi 108". TgpchlY Dupc Ldm sang loa.ll^'ir St, 3;tr5-8
2. Marlcna. C. Kruger, Linda M vd cs (2010).
"Tdc dyng cda stta tdng cudng Canxi vd Vitamin D dii vdi tinh trang Vitamin D vd chu chuyin xuong d phy ntt mdn kinh Ddng Nam A". Tdi lieu Hgi nghi, Hgi lodng xuong Tp Hi Chl Minh, tr 55-ti-70
3. Cabrera, CD el al (1998)." Biochemical markers of bone formation in the study of postmenopausal osteoporosis". Osteoporos to.; 8(2): 147-51
4. Christiansen. C, Riis BJ, Rodbro P (1987).
"Prediction of rapid bone loss in postmenopausal women". Lancet, 1:1:1105-8 5. Gamero.P et al. (2001)." Evaluation of a
Fully Automated Serum Assay for C- Terminal Cross-Linking Telopeptide of Type 1 Collagen in Osteoporosis". Clin Chem. Apn 47(4): 694-702
6. Iraj Nabipour el al. (2008),"Reference database of Crosslaps and Osteocalcm for liealtiiy hanian population". Archives of Iranian Medicine, Vol 11, No 2,2008:203-206 7. Pino J D , Gomez EM. et al
(1991). "Influence of sex, age and menopause in serum osteocalcin "(BGP) levels. ./A/o/A&rf; 69(24): 1135-8 8. Weinbrenner. T et al (2003). "Body mass
index and disease duration are predictors of disturbed bone turnover in anorexia nervosa.
Acase- control study". European J of Clin Wuft-irion 57,1262-1267