lteration in mineral amount of bone is a common complication of chronic liver disease.1,2Hepatic osteodystrophy, described by Heaf, is a general definition that describes abnormalities in mineral density
Evaluation of Bone Mineral Density and
Bone Turnover Markers in Patients with
non-Cirrhotic Chronic Hepatitis B
AABBSS TTRRAACCTT OObb jjeecc ttii vvee:: To eva lu a te the bo ne mi ne ral den sity (BMD) and the bi oc he mi cal mar kers of bo ne tur no ver in non-cirr ho tic chro nic he pa ti tis B pa ti ents. MMaa ttee rrii aall aanndd MMeett hhooddss:: We com pa red 1865 ye ars old noncirr ho tic chro nic he pa ti tis B pa ti ents and he althy con trols for BMD and bi -oc he mi cal mar kers of bo ne tur no ver. BMD was me a su red at the lum bar spi ne and the left hip using DXA. RRee ssuullttss:: The re we re 31 he pa ti tis B pa ti ents (19 ma les, 12 fe ma les) and 72 he althy con trols (56 ma les, 16 fe ma les) in the study. The ir me an age was 37.4 ± 10.0 ye ars in the study gro up and 38.5 ± 7.1 ye ars in the con trols. The re we re no dif fe ren ces bet we en the two gro ups for the me an BMD le vels and T sco res. Ho we ver, left hip BMD and T sco res we re sig ni fi cantly lo wer in ma le pa ti ents with chro nic he pa ti tis B in fec ti on when com pa red to ma les in the con trol gro up. Se rum cal ci um, phosp ha te, os te o cal ci ne, in tact pa rath yro id hor mo ne, de oxyp yri di no li ne and 25hydroxy cho le cal ci fe rol le vels did not dif fer bet we en the gro ups. CCoonncc lluu ssii oonn:: In our study, left hip BMD and T sco -res we re fo und to be sig ni fi cantly lo wer in the ma le pa ti ents with chro nic he pa ti tis B in fec ti on when com pa red to ma les in the con trol gro up, ho we ver a sig ni fi cant dif fe ren ce was not de tec ted when all ca ses we re com pa red with the con trol gro up. The re fo re, we sup po se that furt her stu di es on a lar ger po pu la ti on are ne e ded in this is su e.
KKeeyy WWoorrddss:: He pa ti tis B vi rus; chro nic he pa ti tis B; bo ne den sity Ö
ÖZZEETT AAmmaaçç:: Si ro tik ol ma yan kro nik he pa tit B’li has ta lar da ke mik mi ne ral yo ğun lu ğu (KMY) ve ke -mik dön gü sü bi yo kim ya sal pa ra met re le ri ni de ğer len dir mek tir. GGee rreeçç vvee YYöönn tteemm lleerr:: Yaş la rı 18-65 ara sın da olan, si ro tik ol ma yan kro nik he pa tit B’li has ta la rın ve sağ lık lı ol gu la rın KMY ve ke mik dön gü sü bi yo kim ya sal pa ra met re le ri ni kar şı laş tır dık. KMY öl çü mü, DXA yön te mi ile lom ber omur -ga ve sol kal ça böl ge sin den ya pıl dı. BBuull gguu llaarr:: Ça lış ma ya 31 he pa tit B has ta sı (19 er kek, 12 ka dın) ve 72 sağ lık lı ki şi (56 er kek, 16 ka dın) alın mış tır. Yaş or ta la ma sı kro nik he pa tit B’li grup ta 37,4±10 yıl, sağ lık lı kon trol gru bun da 38,5±7,1 yıl ola rak he sap lan dı. Or ta la ma KMY de ğer le ri ve T skor la rı açı sın dan iki grup ara sın da an lam lı fark sap tan ma dı. An cak, sol kal ça KMY ve T skor la rı kro nik he pa -tit B’li er kek has ta lar da kon trol gru bun da ki er kek le re gö re an lam lı öl çü de da ha dü şük bu lun muş tur. Se rum kal si yum, fos fat, os te o kal sin, ak tif pa rat hor mon, de ok si pi ri di no lin ve 25-hid rok si kal si fe rol se vi ye le ri yö nün den iki grup ara sın da an lam lı fark sap tan ma mış tır. SSoo nnuuçç:: Ça lış ma mız da kro nik he pa tit B’li er kek has ta la rın sol kal ça KMY ve T skor la rı sağ lık lı er kek le re gö re an lam lı dü zey de dü şük bu lun muş tur an cak tüm va ka lar kon trol gru bu ile kar şı laş tır dı ğın da an lam lı bir fark sap tan ma -mış tır. Bu ne den le bu ko nu da da ha ge niş va ka grup la rı ile ya pı la cak ile ri ça lış ma la ra ge rek ol du ğu nu dü şün mek te yiz.
AAnnaahh ttaarr KKee llii mmee lleerr:: He pa tit B vi rü sü; kro nik he pa tit B; ke mik yo ğun lu ğu
TTuurrkkiiyyee KKlliinniikklleerrii JJ MMeedd SSccii 22001122;;3322((22))::332244--3300
Güven ÇELEBİ, MD, Assoc.Prof.,a
Selda SARIKAYA, MD, Assoc.Prof.,b
Şenay ÖZDOLAP, MD, Assoc.Prof.,b
Görkem MUNGAN, MD, Assoc.Prof.,c
Handan ANKARALI, Dr, Prof.,d
Yavuz ÇELİK, MD, Msc,e
Deniz AKDUMAN, MD, Prof.a
Departments of
aInfectious Diseases and
Clinical Microbiology,
bPhysical Medicine and Rehabilitation, cBiochemistry,
Zonguldak Karaelmas University Faculty of Medicine, Zonguldak
dDepartment of Biostatistics,
Düzce University Faculty of Medicine, Düzce
eDepartment of Infectious Diseases and
Clinical Microbiology, Kütahya State Hospital, Kütahya Ge liş Ta ri hi/Re ce i ved: 16.01.2011 Ka bul Ta ri hi/Ac cep ted: 27.11.2011 Ya zış ma Ad re si/Cor res pon den ce: Güven ÇELEBİ, MD, Assoc.Prof. Department of Infectious Diseases and Clinical Microbiology,
Zonguldak Karaelmas University Faculty of Medicine, Zonguldak, TÜRKİYE/TURKEY
guvencelebi@yahoo.com
doi: 10.5336/medsci.2011-22718
and bo ne me ta bo lism in in di vi du als with chro nic li -ver di se a se.3Pre va len ce of os te o po ro sis has be en re-por ted bet we en 9% and 100% among the pa ti ents with chro nic li ver di se a ses in which cho les ta tic di s-or ders and al co ho lic li ver di se a se ha ve the hig hest ra tes.4-8 Im ba lan ce bet we en os te ob last-me di ta ted bo ne for ma ti on and os te oc last-in du ced bo ne re sorpti on is con si de red as the ma in mec ha nism of os te o -po ro sis in prog res si ve li ver di se a se.1,2The ele ments in po ten ti al mec ha nism of bo ne loss in prog res si ve li ver di se a se are hypot he si zed as hypo go na dism (estro gen and tes tos te ro ne de fi ci ency), re du ced he pa -tic hydroxy la ti on of vi ta min D, re du ced os te ob las -tic ac ti vity as so ci a ted with im pa i red he pa tic pro duc ti on of in su linli ke growth fac tor1, in cre a sed os te -oc las tic ac ti vity du e to im pa i red he pa tic pro duc ti on of os te op ro teg rin and in cre a sed le vel of pro inf lam -ma tory cyto ki nes.1,2Os te odys trophy in pa ti ents with li ver cirr ho sis se con dary to vi ral he pa ti tis has be en well de fi ned; ho we ver, the re is litt le in for ma ti on abo ut oc cur ren ce of bo ne di se a se in non-cirr ho tic pa ti ents with chro nic vi ral he pa ti tis, es pe ci ally in asym pto ma tic he ma ti te B vi rus (HBV) car ri ers.9-13 The re fo re, the aim of this study was to eva lu a te the bo ne mi ne ral den sity (BMD) and the bi oc he mi cal mar kers re le vant the bo ne tur no ver in noncirr ho -tic pa ti ents with chro nic vi ral he pa ti tis B.
MA TE RI AL AND MET HODS
This pros pec ti ve study was con duc ted ac cor ding to the “Dec la ra ti on of Hel sin ki-Et hi cal Prin cip les for Me di cal Re se arch In vol ving Hu man Sub ject s” in Zon gul dak Uni ver sity Hos pi tal. The study pro to -col was ap pro ved by et hi cal com mit te e of our hos-pi tal and a writ ten in for med con sent was ob ta i ned from each sub ject. We com pa red 18-65 ye ars old non-cirr ho tic chro nic he pa ti tis B pa ti ents and agegen der ad jus ted he althy con trols for BMD and bi -oc he mi cal mar kers of bo ne tur no ver. The con trol gro up con sis ted of the sub jects who we re ran domly se lec ted from an ot her wi se he althy po pu la ti on aged bet we en 1865 ye ars and had a ne ga ti ve se ro -logy for HIV, HCV and HBsAg.
Chro nic he pa ti tis B was de fi ned as be ing po si -ti ve for HBsAg for mo re than six months. The ca se gro up was con sis ted of the chro nic he pa ti tis B pa ti
-ents who we re eva lu a ted with de ta i led cli ni cal ex-a mi nex-a ti on, ex-ab do mi nex-al ul trex-a so nog rex-aphy (USG), ex-and ro u ti ne la bo ra tory me a su re ments with 6-12 months in ter vals in our ins ti tu ti on. An inac ti ve HBsAg car-ri er was de fi ned as a pa ti ent who had be en po si ti ve for HBsAg for mo re than six months, had per sis tently nor mal ALT le vels on re pe a ted me a su re -ments du ring a fol low-up pe ri od of at le ast one ye ar and a ne ga ti ve or a low le vel (<104 copy/ml) of HBV-DNA.14,15Li ver bi opsy was not ro u ti nely im-p le men ted for the im-pa ti ents with chro nic he im-pa ti tis B, ho we ver, pa ti ents who had ele va ted ALT le vels (1.5 or mo re ti mes hig her than the up per li mit of nor mal va lu e) or high le vel of HBV-DNA (≥ 104copy/ml) we re eva lu a ted with a li ver bi opsy. Chro nic he pa ti -tis B pa ti ents who we re di ag no sed as cirr ho sis with li ver bi opsy or who had any fin ding (cli ni cal, la bo -ra tory or ima ging) com pa tib le with li ver cirr ho sis we re not inc lu ded in this study.
Exc lu si on cri te ri a: The pa ti ents in the ca se gro -up who we re con cur rently po si ti ve for HIV, HCV or HDV we re exc lu ded. The par ti ci pants of the study who had a po si ti ve his tory of the fol lo wing syste mic di se a ses and di sor ders we re exc lu ded eit her from the ca se gro up or the con trol gro up: di a be tes mel li tus, chro nic re nal di se a se, thyro id di se a ses, pa rath yro id di se a ses, cur rent or pre vi o us ma lig nancy, con nec ti ve tis su e di se a ses, cur rent or pre vi o us al co hol abu se, pre vi o usly di ag no sed os te o po ro sis, be ing on me di ca ti ons for os te o po ro sis, hor mo ne the rapy or any me -di ca ti on af fec ting bo ne me ta bo lism such as ste ro ids, an ti-epi lep tics, he pa rin etc. Post me no pa u sal fe ma les we re al so exc lu ded in both gro ups.
BO NE MI NE RAL DEN SITY ME A SU RE MENTS
Bo ne mi ne ral den sity was me a su red at the lum bar spi ne (L1-4) and the left hip (to tal hip) using DXA (Ho lo gic QDR4500W, Ho lo gic, Inc Bed ford, USA). The re sults we re me a su red on g/cm2and the number of stan dard de vi a ti on (SD) ba sed on a com pa ri -son with pe ak bo ne mass (T sco re). The pre ci si on er ror for the lum bar spi ne, hip and fo re arm we re 1% for all re gi ons. For qu an ti fi ca ti on of bo ne mass loss, World He alth Or ga ni za ti on (WHO) cri te ri a which we re de fi ned for post me na u po sal wo men was used:16Nor mal BMD is de fi ned as BMD < -1
SD be low me an nor mal yo ung adult BMD, os te o -pe ni a is de fi ned as BMD bet we en -1 and -2.5 SD be low me an nor mal yo ung adult BMD and os te o -po ro sis is de fi ned as BMD > -2.5 SD be low me an nor mal yo ung adult BMD.
BI OC HE MI CAL ME A SU RE MENTS
Blo od was drawn in the mor ning af ter an over night fas ting. Se rum was analy zed for glu co se, cal ci um (Ca), phosp ha te (P), al ka li ne phosp ha ta se (ALP), ala ni ne ami no trans fe ra se (ALT), as par ta te ami no trans fe ra se (AST)and ure a, and uri ne and se rum cre a ti ni ne spec trop ho to met ric analy sis was per for -med with Co bas In teg ra 800 (Roc he Di ag nos tics, Mann he im, Ger many). Fre e T3, fre e T4, TSH and in tact pa rath yro id hor mo ne (iPTH) le vels we re me a su red using che mi lu mi nes cent im mu no met ric as say with Im mu li te 2000 (Bi oDPC, LA, US). Os te -o cal ci ne was me a su red using che mi lu mi nes cent im mu no met ric as say with Im mu li te One (Bi oDPC, LA, US). De oxyp yri di no li ne (DPD) was me a su red using che mi lu mi nes cent enz yme la be led as say with Im mu li te One ( Bi oDPC, LA, US). DPD and uri ne cre a ti ni ne (UCr) was me a su red using the se cond mor ning uri ne or from 24-h col lec ti on spe ci mens using stan dar di zed com mer ci al as says. To cor rect for va ri a ti ons in uri nary flow, DPD re sults sho uld be nor ma li zed ac cor ding to the uri nary cre a ti ni ne con cen tra ti on, and ex pres sed as na no mo les DPD, per li ter di vi ded by mi li mo les cre a ti ni ne per li ter (nM DPD/ mM cre a ti ni ne)(Uri nary ex cre ti on was ex pres sed as the ra ti o of DPD to UCr.) 25-hydrox-y cho le cal ci fe rol [25(OH) D3] (Im mun di ag nos tik AG, Bens he im and Bi o me di ca,Wi en) was me a su red by com pe ti ti ve ELI SA as says with LP400 ELI -SA (Pas te ur Di ag nos tics,FR) system. All samp les we re sto red at -70oC un til tes ted.
STA TIS TI CAL ANALY SIS
Des crip ti ve va lu es we re cal cu la ted as me an±stan -dad de vi a ti on (SD), co unt and per cent. Nor ma lity test we re do ne for con ti nu o us va ri ab les by using Kol mo go rov-Smir nov test. Af ter that, stu dent t-test or Mann Whit ney U test for two in de pen dent two gro ups and Pe ar son Chi-squ a re test we re used first be ca u se unad jus ted p va lu es we re ob ta i ned. Af ter,
Co va ri an ce analy sis was used for dif fe ren ces bet -we en gro ups, sex and its in te rac ti ons on mar kers of bo ne me ta bo lism for ad jus ting p va lu es we re ob ta -i ned. In th-is analy s-is age, body mass -in dex (BMI), smo king, al co hol in ta ke, da ily cal ci ums in ta ke, ALT, AST, ALP, glu co se, ure a, cre a ti ne, Ca, P, TSH, fre e T3 and fre e T4 we re ac cep ted co va ri a tes. Type I er ror pro ba bi lity was ac cep ted as 5%.
RE SULTS
The re we re 31 (19 ma les, 12 fe ma les) pa ti ents with chro nic he pa ti tis B in the ca se gro up and 72 (56 ma -les, 16 fe ma les) he althy in di vi du als in the con trol gro up. All fe ma les in both gro ups we re pre me no pa u sal. In ca se gro up, 28 pa ti ents we re HBe Ag ne -ga ti ve and an ti-HBe Ag po si ti ve and the re ma i ning thre e we re HBe Ag po si ti ve and an tiHBe Ag ne ga ti -ve. Among he pa ti tis B pa ti ents, 28 we re inac ti ve HBsAg car ri ers and the re ma i ning thre e had mild he pa ti tis ac cor ding to Kno dell his to lo gi cal ac ti vity sco re in li ver bi opsy. The me an age was 37.4±10.0 ye ars in ca se gro up and 38.5±7.1 ye ars in the con-trols. The re we re sta tis ti cally sig ni fi cant dif fe ren ces bet we en the me an va lu es of (ca ses and con trols re-s pec ti vely) AST (27.2±13.4 and 20.0±5.0 U/L, p<0.001), ure a (23.7±6.4 and 28.2±7.4 mg/dL, p=0.004), fre e T3 (3.50±0.4 and 2.0±0.3 pg/mL, p<0.001), TSH (1.23±0.9 and 1.65±1.2 µIU/mL, p=0.027) and fre e T4 (1.19±0.2 and 0.89±0.2 ng/dL, p<0.001). Ho we ver, TSH, fre e T3 and fre e T4 le vels we re all in nor mal ran ge in both gro ups. In he pa ti -tis B gro up, da ily cal ci um in ta ke was in suf fi ci ent for 83.9% of the ca ses whe re as in suf fi ci ent da ily cal ci -um in ta ke was evi dent in 26.4% of the con trols and the dif fe ren ce was sta tis ti cally sig ni fi cant (p<0.001). De mog rap hic fe a tu res and the ba se li ne va lu es of se rum bi oc he mi cal pa ra me ters of the he pa ti tis B pa -tents and the con trols are shown in Tab le 1.
COM PA RI SONS OF BI OC HE MI CAL MAR KERS OF BO NE TUR NO VER
The me an se rum iPTH le vels in the ca ses and the con trols we re 48.9±16.8 and 40.0±14.7, res pec ti -vely. The dif fe ren ce was sta tis ti cally sig ni fi cant with stu dent-T test (p=0.010); ho we ver, it was not with co va ri an ce analy sis (p=0.918). The re was a
sta tis ti cally sig ni fi cant dif fe ren ce in the me an DPD le vels bet we en the ca ses and the con trols (7.2±2.6 and 6.1±1.8, res pec ti vely) with stu dent-T test (p=0.020). Ho we ver, the dif fe ren ce was not sta tis -ti cally sig ni fi cant with co va ri an ce analy sis (p=0.557). The me an va lu es of İPTH and 25(OH)D3 we re not sta tis ti cally sig ni fi cant dif fe rent bet we en the gro ups (Tab le 2).
COM PA RI SONS OF BMD ME A SU RE MENTS
The me an va lu es of lum bar spi ne BMD in chro nic he pa ti tis B pa ti ents and in con trols we re si mi lar (1.017±0.1 and 1.049±0.1, res pec ti vely). No sta tis ti -cally sig ni fi cant dif fe ren ces we re de tec ted bet we en the gro ups in com pa ri sons of lum bar spi ne T so re, to tal fe mur BMD or to tal fe mur T sco re (Tab le 2).
In com pa ri sons for each gen der se pa ra tely (ma le ver sus ma le and fe ma le ver sus fe ma le), the re was no sig ni fi cant dif fe ren ce bet we en the fe ma les of the two gro ups; ho we ver in ma les, to tal fe mur BMD (0.990 ver sus 1.176 p=0.007) and to tal fe mur T sco re (-0.29 ver sus 0.92, p=0.009) we re hig her in ma le con trols. The dif fe ren ces we re sta tis ti cally sig ni fi cant with co va ri an ce analy sis (Tab le 3).
DIS CUS SI ON
The mec ha nism of os te o po ro sis as so ci a ted with chro nic li ver di se a se is not comp le tely un ders to od, ho we ver as in se ni le os te o po ro sis, im ba lan ce bet -we en os te ob last-me di ta ted bo ne for ma ti on and os-te oc last-in du ced bo ne re sorp ti on is be li e ved to be the ma in re a son of os te o po ro sis in chro nic li ver di
s-Chronic Hepatitis B patients Control group
(n=31) (n=72)
Variable Mean±SD, (min-max) or (%) Mean±SD, (min-max) or (%) p value
Age 37.4±10.0 (20-54) 38.5±7.1 (26-58) 0.524 Sex 0.086 Male 19 (61.3%) 56 (77.8%) Female 12 (38.7%) 16 (22.2%) BMI (kg/m2) 24.89±3.5 (13.60-30.50) 26.78±4.1 (19-37.5) 0.027 Smoking 11/31 (35.5%) 17/72(23.6%) 0.218 Alcohol use 5/31(16.1%) 3/72(4.2%) 0.038 Daily Ca intake <0.001 Insufficient 26 (83.9%) 19 (26.4%) Medium 5 (16.1) 36 (50.0%) Sufficient 0 (0%) 2 (2.8%) ALT 33.3±27.1 (8-124) 25.6±11.8 (9-69) 0.386 AST 27.2±13.4 (14-77) 21.0±5.0 (9-34) <0.001 ALP 68.8±23.6 (34-145) 73.9±27.9 (32-249) 0.377 Glucose 89.6±13.8 (70-153) 93.9±11.4 (73 -155 ) 0.101 Urea 23.7±6.4 (10-40 ) 28.2±7.4 ( 4-48) 0.004 Creatinine 0.7±0.2 (0.5-1.1) 0.8±0.1 (0.3-1.2) 0.57 Calcium 9.5±0.5 (7.7 - 10.2) 9.6±0.5 (7.8-10.6) 0.915 Phosphate 3.3±0.5 (2.5-4.5) 3.3±0.6 (1.9-5.0) 0.648 TSH 1.23±0.9 (0.36-4.50) 1.65±1.2 (0.36-5.00) 0.027 Free T3 3.50±0.4 (2.20-4.20) 2.00±0.3 (1.56-3.36) <0.001 Free T4 1.19±0.2 (0.8-1.60) 0.89±0.2 (0.8-1.95) <0.001
TABLE 1: Demographic characteristics and the mean values of serum biochemical parameters of the
hepatitis B patients and the controls.
ALT (normal range < 42 U/L), AST (normal range < 37 U/L, ALP (normal range for females 35-108 IU/L, for males 40-129 IU/L), glucose (normal range 70-110 mg/dL), urea (normal range 10-50 mg/dL,) creatinine (normal range(0,5-1,2 mg/dL), calcium (normal range 8.4-10.2 mg/dL), phosphate (normal range 2.5-4.5 mg/dL), TSH (normal range 0.4-5.0 µIU/mL), free T3 (normal range 1.6-4.7 pg/mL), free T4 (normal range 0.8-1.9 ng/dL). SD: Standard deviation; BMI: Body mass index.
e a se.1,2Mul tip le mec ha nisms that ca u se bo ne loss we re des cri bed in dif fe rent types of li ver di se a ses. For ins tan ce, ele va ted le vels of in ter le u kin-17 which in du ces os te oc las tic ac ti vity is con si de red to be res pon sib le of bo ne loss in al co ho lic li ver di se a -se or on co fe tal fib ro nec tin pro du ced by ac ti va ted stel la te cells are sug ges ted to sup press os te ob lasts and bo ne for ma ti on in pa ti ents with pri mary bi li -ary cirr ho sis. The po ten ti al mec ha nism of bo ne loss in non-cirr ho tic chro nic he pa ti tis B is not cle arly known. Ho we ver, so me stu di es ha ve sug ges ted that
ele va ted le vels of se rum cyto ki nes as so ci a ted with vi ral he pa ti tis, such as tu mor nec ro sis fac tor-alp ha, in ter le u kin1 and in ter le u kin6 may in hi bit os te ob lastme di a ted bo ne for ma ti on or pro mo te os te -oc last-in du ced bo ne re sorp ti on which fi nally le ad to re du ced BMD.1,2
Os te odys trophy in pa ti ents with li ver cirr ho sis se con dary to vi ral he pa ti tis has be en well de fi ned, ho we ver the re is li mi ted num ber of the pub lis hed stu di es that in ves ti ga te bo ne me ta bo lism in pa ti ents with non-cirr ho tic vi ral he pa ti tis (es pe ci ally in
Chronic Hepatitis B patients Control group
(n=31) (n=72) Unadjusted p value Adjustable p value Variable* mean±SD min-max) mean±SD (min-max) according to student-T test according to Covariance analysis
Osteocalcine 8.7±5.5 (1.2-21.3) 8.0±4.5 (1.0-25.8) 0.541 0.616
iPTH 48.9±16.8 (19.9-84.0) 40.0±14.7 (17.0-77.5) 0.010 0.918
DPD 7.2±2.6 (2.8-15.0) 6.1±1.8 (3.2-13.4) 0.020 0.557
25(OH)D3 64.9±61.0 (2.7-227.0) 41.9±49.9 (1.6-202.0) 0.080 0.216
Lumbar spine BMD (g/cm2) 1.017±0.1 (0.751-1.260) 1.049±0.1 (0.847-1.443) 0.182 0.141
Lumbar spine T score -0.50±1.0 (-3.1-1.7) -0.27±1.0 (-2.2-3.2) 0.281 0.174 Total femur BMD (g/cm2) 0.969±0.1 (0.718-1.326) 1.037±0.1(0.705-1.358) 0.030 0.344
Total femur T score -0.20±0.9 (-1.9-1.9) 0.14±0.9 (-1.9-2.1) 0.076 0.491
TABLE 2: Comparisons of bone metabolism markers and BMD values between the hepatitis B patients and the controls.
Osteocalcine (normal range 3.1-13.7 ng/mL). iPTH (normal range 10-87 pg/mL), DPD (normal range for male 2.3-5.4 for female 3.0-7.4 nM DPD/ mM creatinine), [25(OH)D3] (normal range 25-125 nmol/L).
* In this analysis age, body mass index, smoking, alcohol intake, daily Ca intake, ALT, AST, ALP, glucose, urea, creatine, Ca, P, TSH, free T3 and free T4 were accepted covariates. SD: Standard deviation.
Male Female
Chronic Hepatitis B Chronic Hepatitis B
patients Control group Adjustable p value patients Control group Adjustable p value (n=19) (n=56) according to (n=12) (n=16) according to Variable* mean±SD mean±SD Covariance analysis mean±SD mean±SD Covariance analysis
Osteocalcine 6.6±2.7 9.8±1.8 0.286 8.4±6.1 11.0±7.5 0.814
iPTH 35.7±9.4 36.3±6.4 0.955 16.5±25.9 68.5±20.9 0.263
DPD 6.4±1.2 6.9±0.9 0.906 3.09±3.5 13.6±4.6 0.281
25(OH)D3 97.1±44.6 52.7±18.6 0.335 100.7±95.4 79.3±110.7 0.383
Lumbar spine BMD (g/cm2) 1.040±0.06 1.182±0.04 0.05 1.043±0.2 0.864±0.2 0.578
Lumbar spine T score -0.44±0.6 0.81±0.4 0.05 0.31±1.3 -2.57±1.5 0.298
Total femur BMD (g/cm2) 0.990±0.06 1.176±0.04 0.007 1.013±0.2 0.706±0.2 0.374
Total femur T score -0.29±0.4 0.92±0.3 0.009 0.62±1.3 -1.89±1.6 0.369
TABLE 3: Comparisons of bone metabolism markers and BMD values between hepatitis B patients and
controls in each sex separately. The table includes the “corrected” mean values of the participants which calculated according to covariance analysis.
* In this analysis age, body mass index, smoking, alcohol intake, daily ca intake, ALT, AST, ALP, glucose, urea, creatine, Ca, P, TSH, free T3 and free T4 were accepted covariates. SD: Standard deviation.
asym pto ma tic HBV car ri ers) in Pub med.9-13 In a study per for med by Tsu ne o ka et al. in 1993-1994, 20 noncirr ho tic sub jects with chro nic vi ral he pa ti tis du e to HBV (n=8) and HCV (n=12) we re com pa -red for bo ne me ta bo lism with cirr ho tic pa ti ents and al so with age-sex matc hed he althy vo lun te ers.9 BMD was sig ni fi cantly dec re a sed in pa ti ents with li ver cirr ho sis and, to a les ser ex tent, in pa ti ents with chro nic he pa ti tis, com pa red with he althy sub-jects. In anot her study, Schi ef ke et al. in ves ti ga ted BMD and bo ne tur no ver mar kers in bi opsy-pro ven non-cirr ho tic 43 pa ti ents (30 with HCV and 13 with HBV) with vi ral he pa ti tis.12They clas si fi ed the pa-ti ents ac cor ding to Kno dell his to lo gi cal sta ging sys-tem and fo und that the BMD was sig ni fi cantly lo wer and iPTH le vel was sig ni fi cantly ele va ted in mo re ad van ced sta ges of li ver di se a se. The study al so de mons tra ted that BMD and Tsco res we re lo -wer in pa ti ents with chro nic he pa ti tis C than in pa ti ents with chro nic he pa ti tis B, but the dif fe ren -ce was not sta tis ti cally sig ni fi cant. In anot her study pub lis hed in 2006, Ye ni ce et al. as ses sed bo ne me-ta bo lism and mi ne ral den sity in 105 non-cirr ho tic chro nic vi ral he pa ti tis pa ti ents (60 HBV and 45 HCV) who we re di ag no sed with li ver bi opsy which sho wed mo de ra te and se ve re he pa ti tis ac ti va ti on with ele va ted se rum ALT le vels (1.5-2 ti mes hig her than nor mal li mits).13They fo und that the me an T sco re (BMD me a su re ments we re per for med at medi al pha lan xes) was sig ni fi cantly hig her and the me -an PTH le vel was sig ni fi c-antly lo wer in ma le pa ti ents bet we en 20-40 ye ars of age with chro nic he pa ti tis B who we re com pa red with agesex matc -hed he althy con trols. The me an P le vel in ma le pa-ti ents bet we en 40-65 ye ars old with chro nic he pa ti tis B and the me an DPD le vel in post me no pa u sal fe ma le pa ti ents with chro nic he pa ti tis B we -re sig ni fi cantly lo wer when com pa -red with age-sex matc hed he althy con trols. The cha rac te ris tics of the pa ti ents, the eti o lo gic agents of chro nic he pa ti tis (HBV or HCV), the sta ge of the li ver di se a se (mild to se ve re) and the mo del of sta tis ti cal analy sis had so me he te ro ge ne ity in the abo ve stu di es and in the pre sent study. Our study was per for med only on the pa ti ents with he pa ti tis B, and 28 of them we re inac -ti ve HBV car ri ers whe re as thre e of them had mild
he pa ti tis. The re fo re, com pa ring the re sults of the pre vi o us stu di es and the cur rent study may ha ve so -me li mi ta ti ons. Ho we ver, in con trast to Ye ni ce et al.’s study, the me an va lu e of to tal fe mur BMD and the me an va lu e of to tal fe mur T sco re we re sig ni fi -cantly lo wer in ma les with inac ti ve he pa ti tis B in the cur rent study.13The me an va lu e of iPTH le vels was sig ni fi cantly ele va ted in the chro nic he pa ti tis (B and C) pa ti ents with mo re ad van ced sta ges of li -ver di se a se in Schi ef ke et al.’s re port.12Si mi larly, iPTH and DPD le vels we re sig ni fi cantly hig her in pa ti ents with inac ti ve he pa ti tis B in our study. Ho we ver, the dif fe ren ce was not sta tis ti cally sig ni fi -cant when the sta tis ti cal analy sis was per for med with co va ri an ce mo del in our study.
In a re cently pub lis hed study, Lo Re III et al. com pa red 625 HIV sub jects coin fec ted with he pa -ti -tis B or he pa -ti -tis C with 612 age-sex ad jus ted HIV mo no-in fec ted in di vi du als for BMD sco res.17The me an BMD Z sco res at the lum bar spi ne and fe mo -ral neck we re lo wer among he pa ti tis-co-in fec ted wo men com pa red to HIV-mo no-in fec ted wo men eit her wit ho ut ad just ment or af ter ad just ment in sta tis ti cal met hod. In con trast to wo men, no dif fe -ren ces for BMD Z so res (wit ho ut ad just ment or af ter ad just ment) we re ob ser ved among mo noin -fec ted and co-in -fec ted men. In our study, ho we ver not sta tis ti cally sig ni fi cant, the me an T sco re (lumbar spi ne or to tal fe mur) in the pa ti ents with he pa -ti -tis B was lo wer than in he alth in di vi du als. When com pa red each sex se pa ra tely, the me an ad jus ted fe mur T sco re in the ma le pa ti ents with he pa ti tis B was lo wer than in the he althy ma les (p=0.009) whi -le a sig ni fi cant dif fe ren ce for the me an T sco re was not ob ser ved bet we en the he althy wo men and the wo men with he pa ti tis B.
Chro nic inf lam ma tory con di ti ons may sti mu la te ac ti va ti on of so me cyto ki nes such as TNFalp -ha, IL-1, IL-3, IL-6, IL-7, IL-11, IL-13, IL17 etc.1,2 In many stu di es se rum cyto ki ne le vels in the pa ti -ents with HBV in fec ti on (asym pto ma tic HBV car-ri er or chro nic he pa ti tis B or acu te he pa ti tis B) we re de tec ted to be hig her than in he althy do -nors.18,19In our study, the me an BMD and T sco res we re fo und to be lo wer in the ma le pa ti ents with he pa ti tis B than in the he althy ma les. Se rum cyto
-ki ne le vels in the sub jects we re not in ves ti ga ted, ho we ver the pos sib le mec ha nism of low BMD and T sco res in the ma le pa ti ents with he pa ti tis B in our study may be as so ci a ted with ele va ted cyto ki ne le -vels du e to chro nic inf lam ma ti on in li ver.
The re are so me li mi ta ti ons in our study. The num ber of the sub jects is re la ti vely small, li ver bi -opsy was not per for med in most of the sub jects and se rum cyto ki ne le vels of the pa ti ents we re not de-ter mi ned. Ho we ver; the cur rent study ser ves so me clu es sug ges ting that pa ti ents with chro nic HBV
in-fec ti on, even in the asym pto ma tic car ri er sta tus, may ha ve an in cre a sed risk for al te ra ti on of bo ne me ta bo lism. The re fo re, we sup po se that furt her stu di es are ne e ded in this is su e.
A
Acckk nnooww lleeddgg mmeenntt
We thank Si bel Ki ran (from the De part ment of Pub lic He alth) for her con tri bu ti ons abo ut da ta analy sis and Pe ri han Sap maz (from the De part ment of Physi cal Me di -ci ne and Re ha bi li ta ti on) for her con tri bu ti ons du ring da ta col lec ti on.
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