High incidence of vertebral osteoporotic fracture within the first year after liver transplantation

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1 High incidence of vertebrl osteoporotic frcture within the first yer fter liver trnsplnttion S. Butin 1, I. Griffoul 1, F. Espitlier 2, E. Slmé 3,4, D. Mullemn 1,4, P. Goupille 1,4 1 Deprtment of Rheumtology, 2 Deprtment of Anesthesi nd Intensive Cre, 3 Deprtment of Heptobiliry Surgery nd Trnsplnttion, CHRU de Tours, Frnce; 4 Université Frnçois-Rbelis de Tours, Frnce. Abstrct Objective Bone loss is compliction for ptients with liver diseses nd fter trnsplnttion, which results in incresed frcture risk. The im of this study ws to determine the incidence of osteoporotic vertebrl frctures following liver trnsplnttion. Methods We performed prospective study of ptients who were witing liver trnsplnttion. Ptients were seen t bseline (visit 1) nd one yer fter trnsplnttion (visit 2). At ech visit, risk fctors of osteoporosis were collected, biochemicl tests were performed nd bone minerl density with Vertebrl Frcture Assessment ws ssessed. Results One hundred nd fifteen ptients were in the pre-trnsplnt group nd 33 ptients were in the post-trnsplnt group. In the pre-trnsplnt group, the prevlence of vertebrl frctures ws 23.5%. The prevlence of densitometric osteoporosis ws higher t the lumbr spine thn t the femorl neck. In the post-trnsplnt group, the prevlence of vertebrl frctures t visit 1 nd visit 2 ws 33.3% nd 60.6%, respectively with n incidence of 23.1 frctures per 100 ptient-yers. Conclusion Bone frgility ws highly prevlent before trnsplnttion nd worsens one yer fter trnsplnttion. Bone sttus should be evluted in ptients with liver diseses before trnsplnttion to identify ptients t high risk of frcture nd help clinicins to prescribe pproprite preventive cre. Key words osteoporosis, bone minerl density, spinl frcture, liver trnsplnttion, end stge chronic liver disese Clinicl nd Experimentl Rheumtology Clinicl 2017 nd Experimentl Rheumtology 2017; 35:

2 Srh Butin, MD Isbelle Griffoul, MD Fbien Espitlier, MD Ephrem Slmé, MD, PhD Denis Mullemn, MD, PhD Philippe Goupille, MD, PhD Plese ddress correspondence to: Dr Isbelle Griffoul, Deprtment of Rheumtology, Centre Hospitlier Universitire de Tours, Tours cedex 9, Frnce. E-mil: Received on September 9, 2016; ccepted in revised form on Mrch 7, Copyright Clinicl nd Experimentl Rheumtology Competing interests: none declred. Introduction Bone loss is well-known compliction of orgn trnsplnttion prticulrly in ptients witing liver trnsplnttion nd during the first yer fter trnsplnttion (1-3). This bone frgility increses the risk of severe frctures, which themselves increse morbidity nd mortlity (4-6). The mechnisms of this bone frgility re complex nd poorly understood. Heptic osteodystrophy, term tht encompss osteomlci nd osteoporosis is used to describe bone diseses in ptients with chronic liver diseses (7). Chronic liver diseses such s cholesttic liver disese, cholngitis primry sclerosing, lcoholic cirrhosis, heptitis C infection nd hereditry hemochromtosis re ssocited with bone loss. Thus, the incidence of osteoporotic frctures in trnsplnt ptients depends on the severity nd durtion of the underlying liver disese on the one hnd, nd on bone sttus before trnsplnttion, on the other hnd. The prevlence of osteoporotic frcture in the yer following trnsplnttion vries from 22 to 65% of ptients (8, 9). The im of the present study ws to determine the incidence of osteoporotic frctures one yer fter liver trnsplnttion. The secondry objective ws to describe bone turnover nd bone minerl density (BMD) in liver trnsplnt ptients. Methods Ptients nd study design We included prospectively ll ptients witing liver trnsplnttion in the deprtment of liver surgery t the University hospitl of Tours, Frnce, between September 2011 nd July Cndidte for multiple trnsplnttions (liver nd kidney or lung) were excluded. This study ws registered with the ntionl medicines gency: A The protocol nd the clinicl dt collection were pproved by our ethics committee nd institutionl review bord. Dt collection The following chrcteristics were collected t bseline (visit 1): ge, sex, weight (kg), height (cm), relevnt medicl history (i.e. dibetes mellitus, thyroid disese, neoplsi nd HIV infection) nd underlying liver disese (lcoholic cirrhosis, virl heptitis, metbolic diseses (hemochromtosis, glycogen storge disese), utoimmune heptitis, drug-induced liver-injury, heptocellulr crcinom). Risk fctors for bone frgility such s personl history of frcture, history of frcture of the proximl femur in first degree reltive, corticosteroids use 7.5 mg /d of prednisone for 3 months, drug inducing bone frgility, pst or current smoking, pst or current lcoholism, endocrinopthy, dily intke of clcium estimte (norml, 850 mg/d) nd Frdellone questionnire (norml 1000 mg/d) (10), ge t menopuse nd hormone replcement therpy, were collected. Blood tests were systemticlly performed t ech visit including clcium (norml, mmol/l), phosphte (norml, mmol/l), cretinine (norml <100 μmol/l), cretinine clernce (ml/min) ccording to MDRD or Cockroft (renl function ws clssified s impired if clernce <60 ml/min), lnine minotrnsferse (ALT) (norml, 5 35 UI/L) nd sprtte minotrnsferse (AST) (norml, UI/L), lbumin (norml, g/l), proteins (norml, g/l), osteoclcin ssy by ELISA kit (IDS-isys) (norml, ng/ml), CTX ssy by ELISA kit (ecli-cobs Roche) (norml, μg/l for postmenopusl women nd μg/l for premenopusl women nd men), 25-OH Vitmin D3 (norml, >75 nmol/l), prthyroid hormone (PTH) (norml, pg/ml), thyroid stimulting hormone (TSH) (norml, mui/l). BMD ws mesured t ech visit using dul-energy x-ry bsorptiometry (DXA) t the lumbr spine (vertebre L2 L4) nd t the left femorl neck, expressed in g/cm² (Lunr idxa SN ). World Helth Orgnistion (WHO) criteri were used to define osteoporosis (T-score of -2.5 SD or less) (11). A vertebrl frcture ssessment (VFA) iming t the detection of vertebrl frcture ws performed except for ptients with dorsl nd lumbr spine x-rys performed in the lst 3 months. 914 Clinicl nd Experimentl Rheumtology 2017

3 Follow-up of trnsplnt ptients Ptients who underwent liver trnsplnttion were seen t visit 2, one yer fter trnsplnttion, between July 2013 nd September Clinicl dt, blood tests nd DXA were performed s for visit 1. One dy fter trnsplnttion, ptients with weight between 35 nd 54 kg received corticosteroids dose of 240 mg, those between 55 nd 74 kg received 350 mg, those between 75 nd 94 kg received 450 mg, those between 95 nd 114 kg received 500 mg. Then the dose ws grdully decresed ech dy depending on ptient weight. Eight dys fter trnsplnttion, ech ptient, whtever its weight, received corticosteroids dose of 20 mg. All ptients received tcrolimus or cyclosporine. End points The primry ssessment criterion ws the number of incident vertebrl frctures fter one yer following trnsplnttion. The event ws defined by the occurrence of frcture on x-ry or on VFA. Sttisticl nlysis Continuous vribles were expressed s medin nd interqurtile rnge [IQR: 25% 75%] or men, stndrd devition (± SD) nd minimum - mximum. Ctegoril vribles were expressed s number (percentge). The incidence of vertebrl fctures between trnsplnttion nd visit 2 were expressed s the number of new frctures per 100 ptient-yers. After description of ptient s chrcteristics, trnsplnt ptients were nlysed by compring dt t visit 1 nd visit 2. R softwre ( the R Foundtion for Sttisticl Computing, Vienn, Austri) ws used for nlysis. Continuous vribles were compred using the Wilcoxon test. Ctegoril vribles were compred using the Fisher exct test. Continuous mtched vribles were compred using the Wilcoxon pired-test. Ctegoril mtched vribles were compred using the McNemr test. Results Ptients One hundred nd twenty-one ptients were seen t visit 1. Six ptients were excluded (2 with multiple trnsplnttions, nd 4 with missing blood tests). Thus, 115 pre-trnsplnt ptients were included in this study. Twenty-three ptients died before being trnsplnted nd 59 ptients were still witing for trnsplnttion. Thirty-three trnsplnt ptients were seen t visit 2 between July 2013 nd September The medin time intervl between visit 1 nd liver trnsplnttion ws 9 months [IQR: 5; 10] nd 13 months [IQR: 12; 16] between trnsplnttion nd visit 2. Tble I. Generl chrcteristics of pre-trnsplnt ptients t visit 1. n=115 Demogrphic chrcteristics Femle sex 25 (21.7) Age (yer) 59 [53; 63] Weight (kg) 77 [67; 86] BMI (kg/m²) 27 [23; 30] Medicl history Dibete mellitus 29 (25) Neoplsi other thn HCC 6 (5) HIV infection 1 (0.9) Risk fctors for osteoporosis Personl history of severe frctures 22 (19.1) Fmilil history of upper femur 9 (8.9) frcture Use of lcohol 84 (73.0) Glucocorticoids >7.5 mg/d for over 3 months 12 (10.5) Use of tobcco 73 (63) Dysthyroidism 4 (3.7) Menopuse <40 yers old 2 (1.7) HRT 2 (1.7) Clcium intke <1000 mg/d 89 (77.4) Blood tests Clcium (mmol/l) b 2.3 [2.3; 2.4] Phosphte (mmol/l) 1.1 [1.0; 1.3] AST (IU/L) 54 [38; 81] ALT (IU/L) 33 [23; 57] Clernce <60 ml/min 10 (8.7) Proteins (g/l) 71 [66; 77] Albumin (g/l) 35 [31; 40] 25-OH vitmin D (nmol/l) 29 [17; 45] PTH (pg/l) 31 [23; 48] TSH (mui/l) 2.0 [1.3; 2.8] results re expressed s number (%) or medin [interqurtile rnge]. b lbumin-corrected. BMI: body mss index; HCC: heptocellulr crcinom; HRT: hormone replcement therpy; ALT: lnine minotrnsferse; AST: sprtte minotrnsferse; PTH: prthyroid hormone; TSH: thyroid stimulting hormone. Pre-trnsplnt ptients group (n=115) The min chrcteristics of the 115 pretrnsplnt ptients group re presented in Tble I. Among the 115 ptients, 43 (37.4%) hd lcoholic cirrhosis, 15 (13.1%) hd virl liver disese, 24 (20.9%) hd lcoholic nd virl cirrhosis, 16 (13.9%) hd lcoholic cirrhosis nd non-lcoholic steto-heptitis (NASH), 2 (1.7%) hd utoimmune heptitis, 12 (10.4%) hd other liver diseses, 3 (2.6%) hd primitive heptocellulr crcinom. Twenty-two ptients (19.1%) reported personl history of severe osteoporotic frcture, 2 (1.7%) with vertebrl frcture, 20 (17.4%) with peripherl frcture. Forty-eight (41.7%) ptients hd received one or more drugs tht could ffect bone strength (minly proton pump inhibitors). Blood test results re presented in Tble I. Twenty-six ptients (22.6%) were considered s in the norml rnge for clcium intke nd 10 ptients (8.7%) hd sufficient vitmin D3 level. Three ptients (2.6%) received bisphosphonte before visit 1. Eight ptients (7%) were prescribed with bisphosphonte fter visit 1. The prevlence of vertebrl frctures (on VFA) ws 23.5% (27/115). Bone prmeters re presented in Tble II. Five ptients (4.3%) hd high level of bone turnover. Four ptients (3.5%) hd n isolted increse of bone resorption mrkers nd 5 (4.3%) hd n isolted increse of bone formtion mrkers. The number of osteoporotic ptients in totl, s ssessed by BMD, ws 17/115 (14.8%). The number of osteoporotic ptients ws 10/115 (8.9%) t femorl neck nd 15/115 (13%) t lumbr spine. Trnsplnt ptients group (n=33) The min chrcteristics of the 33 trnsplnt ptients re summrised in Tble III. Medin ge t trnsplnttion ws 59 yers [IQR: 51; 63]. Among the 33 ptients, 13 (39.4%) hd lcoholic cirrhosis, 4 (12.1%) hd virl liver disese, 4 (12.1%) hd lcoholic nd virl cirrhosis, 6 (18.2%) hd lcoholic cirrhosis nd non-lcoholic steto-heptitis (NASH), 1 (3%) hd utoimmune heptitis, 3 (9.1%) hd other liver diseses, 2 (6.1%) hd primitive heptocellulr crcinom. There ws no dif- Clinicl nd Experimentl Rheumtology

4 Tble II. Bone sttus comprison between ptients with nd without vertebrl frcture in pre-trnsplnt ptients. ference in terms of comorbidity nd risk fctor for osteoporosis, between trnsplnt nd pre-trnsplnt ptients groups. At visit 1, 11 (33.3%) ptients hd personl history of severe frcture, 1 (3%) with vertebrl frcture, 10 (30.3%) with non vertebrl frcture. At visit 1, mong the 33 ptients, 14 (42.4%) received t lest one tretment tht could ffect bone strength (minly corticosteroids, 12/14), nd t visit 2, 23 (69.7%) received immunosuppressive drugs. The men cumultive dose of corticosteroid per ptient during the first seven dys post-trnsplnt ws 890 mg. Blood test results re presented in Tble III. At visit 2, 10 ptients (30.3%) were considered s in the norml rnge for clcium intke nd one ptient (3%) hd sufficient vitmin D3 level. None of the ptients received bisphosphonte All ptients, n=115 Ptients with VF, n=18 Ptients without VF, n=97 T-score LS -0.8 [-1.8 ; -0.1] -1.1 [-2.3; -0.6] -0.7 [-1.8; 0.1] BMD LS [0.989; 1.202] [0.901; 1.12] [0.991; 1.223] T-score FN -1.0 [-1.7; 0.1] -1.6 [-2.4; -1.1]* -1.0 [-1.6; -0.1]* BMD FN [0.786; 0.999] [0.710; 0.870]* [0.815; 1.012]* CTX (μg/l) 0.39 [0.26; 0.54] 0.41 [0.33; 0.60] 0.39 [0.24; 0.53] Osteoclcin (ng/ml) b 17 [12; 23] [15.5; 26] 17 [11.9; 22] Results re expressed s medin [interqurtile rnge]. norml vlues for postmenopusl women nd for premenopusl women nd men. b norml vlues *p<0.05. VF: vertebrl frcture; LS: lumbr spine; FN: femorl neck; BMD: bone minerl density (g/cm²). Tble III. Comprison between visit 1 nd visit 2 of trnsplnt ptients. n=33 Visit 1 Visit 2 Demogrphic chrcteristics Weight (kg) 79 [73 ; 88] 78 [67 ; 87] BMI (kg/m²) 28 [24 ; 32] 28 [24 ; 31] Risks fctors of osteoporosis Glucocorticoids >7.5 mg/d for over 3 months 4 (12) 23 (69.7) Clcium intke <1000 mg/d 26 (79) 23 (70) Blood tests Clcium (mmol/l) b 2.3 [2.2; 2.4] 2.3 [2.2; 2.4] Phosphte (mmol/l) 1.1 [1.0; 1.3] 1.1 [0.9; 1.2] AST (UI/L) 52 [39; 71]* 23 [20; 52]* ALT (UI/L) 29 [21; 53] 25 [19; 52] Clernce < 60 ml/min 4 (12) 9 (27) Proteins (g/l) 71 [64; 77] 71 [68; 73] Albumin (g/l) 35 [30; 40]* 41 [40; 45]* 25-OH vit D3 (nmol/l) 29 [17; 48] 36 [28; 50] PTH (pg/l) 29 [21; 37]* 46 [39; 69]* TSH (UI/l) 2.1 [1.5; 3.1] 1.7 [1.1; 2.4] results re expressed s number (%) or medin [interqurtile rnge]. b lbumin-corrected. *p<0.05. BMI: body mss index; ALT: lnine minotrnsferse; AST: sprtte minotrnsferse; PTH: prthyroid hormone; TSH: thyroid stimulting hormone. fter visit 1. Thirty ptients (90.9%) received supplement of vitmin D. The prevlence of vertebrl frctures (on VFA) t visit 1 nd visit 2 were 33.3% (11/33) nd 60.6% (20/33), respectively. Bone prmeters re presented in Tble IV. At visit 1, one ptient hd n isolted increse of bone resorption mrkers nd one hd n isolted increse of bone formtion mrkers. At visit 2, 7 ptients (21.2%) hd n increse of bone turnover mrkers, 9 (27.2%) hd n isolted increse of bone resorption mrkers nd 11 (33.3%) hd n isolted increse of bone formtion mrkers. At visit 1, the number of osteoporotic ptients in totl, s ssessed by BMD, ws 4/33 (12.1%). The number of osteoporotic ptients ws 3/33 (9.1%) t the femorl neck nd 4/33 (12.1%) t the lumbr spine. At visit 2, the number of osteoporotic ptients in totl, s ssessed by BMD, ws 6/33 (18.2%). The number of osteoporotic ptients, s ssessed by BMD, ws 5/33 (15.1%) t the femorl neck nd 4/33 (12.1%) t the lumbr spine. Frcture incidence in trnsplnt ptients (n=33) At visit 2, on VFA, 7 ptients (21.2%) hd t lest one incident vertebrl frcture (5 hd 1 nd 2 hd 2). All were symptomtic nd none of the ptients hd lombr x-ry during the two visits. Among them, 3 lredy hd prevlent vertebrl frcture. Thus, vertebrl frcture incidence ws 23.1 per 100 ptientyers. No peripherl frcture occurred during the study period. Discussion In this monocentric prospective study, the incidence of vertebrl frcture fter liver trnsplnttion ws 23.1 per 100 ptient-yers. The prevlence of vertebrl frctures before nd fter trnsplnttion ws 33.3% nd 60.6%, respectively, so 21.2% of our ptients hd n incident frcture within the 13 months fter trnsplnttion. By contrst, no ptient hd n incident non-vertebrl frcture. Our results re in greement with previous studies reporting tht ptients with severe liver diseses hve bone frgility nd n incresed risk of frcture within the first months fter trnsplnttion (4, 6, 12). In monocentric retrospective study, Krol et l., found frcture incidence of 34% one yer fter trnsplnttion (13). Leidig et l. studied the bone sttus of 235 liver or hert trnsplnt ptients nd found frcture incidence of 25.4% one yer fter trnsplnttion (4). In multivrite nlysis, prevlent vertebrl frctures before trnsplnttion were highly predictive of incident frctures fter trnsplnttion. Guichelr et l. found vertebrl frcture rte of 10%, 18.4% nd 22.3% respectively t 4 months, 1 yer nd 2 yers fter trnsplnttion (12). The cuses of bone loss in trnsplnt ptients re numerous. Immunosuppressnts, including glucocorticoids, ply mjor role (6). For some uthors, mny risk fctors such s ge, femle sex, mlnutrition, low body mss in- 916 Clinicl nd Experimentl Rheumtology 2017

5 Tble IV. Bone sttus comprison between trnsplnt ptients t visit 1 (before trnsplnttion) nd visit 2 (fter trnsplnttion). n=33 Visit 1 Visit 2 T-score LS -0.5 [-1.3; -0.1] [-1.5; -0.17] BMD LS [1.022; 1.181] [1.081; 1.168] T-score FN -0.6 [-1.45; 0.3]* -1.4 [-2.1; -0.6]* BMD FN [0.828; 1.031]* [0.779; 0.974]* CTX serum (μg/l) 0.34 [0.20; 0.50]* 0.49 [0.32; 0.88]* Osteoclcin (ng/ml) b 15.3 [11.3; 21.7]* 30 [23; 47]* Results re expressed s medin [interqurtile rnges]. *p<0.05. norml vlues for postmenopusl women nd for premenopusl women nd men. b norml vlues LS: lumbr spine; FN: femorl neck; BMD: bone minerl density (g/cm²); VF: vertebrl frcture. dex (BMI), pst history of frctures nd cumultive dose of corticosteroids, led to bone frgility in liver trnsplnt ptients. Nerly qurter of trnsplnt ptients in our study hd high level of bone turnover, while none hd before trnsplnttion. Cumultive glucocorticoid dose ws responsible for prt of bone loss by decoupling of bone remodeling, with decrese in bone formtion nd n increse in bone resorption, erly fter trnsplnttion. Guichelr et l. hve studied the mechnisms of bone loss by performing bone biopsies in 33 liver trnsplnt ptients (14). Bone loss ws observed from the time of trnsplnttion to 4 months fter trnsplnttion with decrese in BMD t lumbr spine nd histomorphometric prmeters of bone volume. Mrkers of bone formtion were low during pre-trnsplnttion period nd returned to norml fter trnsplnttion whilst mrkers of bone resorption were incresed before nd fter trnsplnttion. The uthors hve shown n overll improvement in bone metbolism from the fourth month fter trnsplnttion with return to blnced bone remodelling. In our study, there ws n increse in bone formtion mrkers nd bone resorption one yer fter trnsplnttion. The increse in bone resorption hs lso been ttributed to secondry hyperprthyroidism but this mechnism ppers to be now questionble (15). We observed significnt increse in PTH concentrtions fter liver trnsplnttion while 32 of our ptients were receiving vitmin D, explining the increse tendency in 25-OH vitmin D3 concentrtions, lthough below the norml vlues, fter trnsplnttion. Two hypotheses my be rised to explin these finding. First, clcineurin inhibitors such s tcrolimus nd cyclosporine, elicit negtive clcium blnce nd therefore n increse in PTH (16). Indeed, these molecules hve n effect on clcium rebsorption in the distl convoluted tubule of the kidney, by cting on the trnsient receptor potentil-vnilloid-5 (TRPV5) tht regultes urinry clcium excretion (17). In ddition, glucocorticoids cuse inhibition of intestinl bsorption nd inhibit tubulr rebsorption of clcium. Intestinl ction of glucocorticoids is ntgonistic of vitmin D nd there is reduction of the expression of specific clcium chnnels in the duodenum. Second, worsening of renl fonction, possibly scribble to immunosuppressnt drugs, my hve resulted in mild increse in PTH (16). In our study, decrese of femorl neck BMD of 8% ws found one yer fter trnsplnttion, while BMD t the lumbr spine remined stble. In monocentric retrospective study, Krol et l. found decrese of BMD t both sites (-2.5% t the lumbr spine nd -6.5% t the femorl neck) 6 months fter liver trnsplnttion with stbilistion until one yer fter trnsplnttion. These results re relted to the difference in proportion of corticl bone nd trbeculr bone between these two sites. The femorl neck is minly composed of corticl bone, wheres the lumbr spine is minly composed of trbeculr bone. Bone sttus ws ssessed one yer fter trnsplnttion which my explin the stbility of the BMD t the lumbr spine. Trbeculr bone is more susceptible to chnge thn corticl bone either before or fter trnsplnttion. After trnsplnttion, the restortion of liver function with reversl of cholestsis, vitmin D deficiency nd hypogondism led to n improvement of the BMD t the lumbr spine. Our study hs severl strengths tht we would like to emphsise here. Our study on pre-trnsplnt ptients is one of the few tht hve nlysed BMD nd vertebrl frctures, s ssessed by VFA, before nd fter liver trnsplnttion. Among trnsplnt ptients, no symptomtic frcture occurred. VFA llowed us to detect significnt number of symptomtic vertebrl frctures. Given our results we believe tht ll physicins should be wre of bone frgility in the context of liver trnsplnttion, evlute bone sttus nd provide lifestyle dvice or pproprite mediction in order to prevent further frctures. For ll ptients witing liver trnsplnttion nd in the 6 first months post trnsplnttion we recommend bone sttus ssessment: risk fctors for bone frgility, BMD with VFA, biologicl prmeters (clcium nd phosphte, PTH, 25 OH vitmin D, renl function, thyroid function nd testosterone in men; bone prmeters re not necessry). Thus, reversible cuses of bone loss my be identifible nd treted. Before liver trnsplnttion, we propose to strt n nti-osteoporotic drug if severe frcture or vertebrl frcture on VFA is found or if T-score <-3. Teitelbum suggests tht bone loss following glucocorticoid tretment is most robust within the first 3 to 6 months (18). Therefore erly fter liver trnsplnttion, in prctice we should strt n nti-osteoporotic drug if corticosteroids re introduced over 3 months. This study hd some limittions. First, the number of post-trnsplnt ptients ws rther low, which limited the interprettion of sttisticl results. Second, the medin time between visit 1 nd trnsplnttion ws n verge of 9 months, which my cuse bis in the results. Indeed, n symptomtic vertebrl frcture, identified by VFA fter liver trnsplnttion, my hve occurred during this period nd not fter trnsplnttion. Third, the use of VFA Clinicl nd Experimentl Rheumtology

6 hs its own limittions since vertebrl frctures re less well detected thn with x-rys, on thorcic spine nd in the cse of scoliosis (19). Finlly, the use of biologicl mrkers of bone remodelling in this popultion cn be discussed for two resons: i) blood smples must be done when fsting nd in the sme lbortory for comprison. Although ll visits were scheduled some ptients my be not be fsting t the time of blood smpling; ii) in ptients with chronic liver disese, mrkers of bone turnover re less relible, due to liver collgen metbolism chnges induced by fibrogenesis, thn in post-menopusl women. In conclusion, ptients with chronic liver disese re t risk of frgility frcture nd this frgility worsens significntly nd rpidly fter trnsplnttion, resulting in subsequent incident vertebrl frctures. It seems essentil to investigte bone sttus extensively nd, if necessry, correct risk fctors or/nd strt nti-osteoporotic tretment. Moreover, close follow-up fter trnsplnttion seems essentil to improve bone helth in this context. Acknowledgments We would like to thnk Nelly Jccz- Vllée, Fbienne Chlier for blood smpling. We thnk the outptient liver trnsplnt nd liver trnsplnt deprtment nd prticulrly Sndr Durte nd Agnès Robert for giving us the list of ptients witing trnsplnttion. We thnk Dr Virginie Mrtillé, Dr Frncine Luféron nd Dr Mthilde Mrot for their contribution in collecting clinicl dt nd performing BMD nd VFA. We re grteful to Prof. Gérrd Chlès nd Dr Slliot for offering their dvice. References 1. EBELING PR: Approch to the ptient with trnsplnttion-relted bone loss. J Clin Endocrinol Metb 2009; 94: DOLGOS S, HARTMANN A, ISAKSEN GA et l.: Osteoporosis is prevlent finding in ptients with solid orgn filure witing trnsplnttion - popultion bsed study. Clin Trnsplnt 2010; 24: STEIN E, EBELING P, SHANE E: Post-trnsplnttion osteoporosis. Endocrinol Metb Clin North Am 2007; 36: LEIDIG-BRUCKNER G, HOSCH S, DODIDOU P et l.: Frequency nd predictors of osteoporotic frctures fter crdic or liver trnsplnttion: follow-up study. Lncet 2001; 357: WIBAUX C, LEGROUX-GEROT I, DHARANCY S et l.: Assessing bone sttus in ptients witing liver trnsplnttion. Joint Bone Spine 2011; 78: HAY JE: Osteoporosis in liver diseses nd fter liver trnsplnttion. J Heptol 2003; 38: GUAÑABENS N, PARÉS A: Liver nd bone. Arch Biochem Biophys 2010; 503: EASTELL R, DICKSON ER, HODGSON SF et l.: Rtes of vertebrl bone loss before nd fter liver trnsplnttion in women with primry biliry cirrhosis. Heptology 1991; 14: PORAYKO MK, WIESNER RH, HAY JE et l.: Bone disese in liver trnsplnt recipients: incidence, timing, nd risk fctors. Trnsplnt Proc 1991; 23: FARDELLONE P, SEBERT JL, BOURAYA M et l.: Evlution of the clcium content of diet by frequentil self-questionnire. Rev Rhum Ml Osteortic 1991; 58: Assessment of frcture risk nd its ppliction to screening for postmenopusl osteoporosis. Report of WHO Study Group. World Helth Orgn Tech Rep Ser 1994; 843: GUICHELAAR MMJ, SCHMOLL J, MALIN- CHOC M, HAY JE: Frctures nd vsculr necrosis before nd fter orthotopic liver trnsplnttion: Long-term follow-up nd predictive fctors. Heptology 2007; 46: KROL CG, DEKKERS OM, KROON HM, RABELINK TJ, vn HOEK B, HAMDY NAT: Longitudinl chnges in BMD nd frcture risk in orthotopic liver trnsplnt recipients not using bone modifying tretment. J Bone Miner Res 2014; 29: GUICHELAAR MM, MALINCHOC M, SIBON- GA JD, CLARKE BL, HAY JE: Bone histomorphometric chnges fter liver trnsplnttion for chronic cholesttic liver disese. J Bone Miner Res 2003; 18: DORE RK: How to prevent glucocorticoid-induced osteoporosis. Cleve Clin J Med 2010; 77: CIPRIANI R, FARIAS MLF: Osteoporosis fter solid orgns trnsplnttion. Arq Brs Endocrinol Metbol 2005; 49: LEE C-T, NG H-Y, LIEN Y-H et l.: Effects of cyclosporine, tcrolimus nd rpmycin on renl clcium trnsport nd vitmin D metbolism. Am J Nephrol 2011; 34: TEITELBAUM S-L: Glucocorticoids nd the osteoclst. Clin Exp Rheumtol 2015; 33 (Suppl. 92): DAMIANO J, KOLTA S, PORCHER R, TOUR- NOUX C, DOUGADOS M, ROUX C: Dignosis of vertebrl frctures by vertebrl frcture ssessment. J Clin Densitom 2006; 9: Clinicl nd Experimentl Rheumtology 2017