Differences in peripartal plasma parameters related to calcium homeostasis of dairy sheep and goats in comparison with cows

Transcription

1 Zurich Open Repository nd Archive University of Zurich Min Lirry Strickhofstrsse 39 CH-8057 Zurich Yer: 2014 Differences in periprtl plsm prmeters relted to clcium homeostsis of diry sheep nd gots in comprison with cows Wilkens, Mirj R; Liesegng, Annette; Richter, Juli; Frser, Dvid R; Breves, Gerhrd; Schröder, Bernd DOI: Posted t the Zurich Open Repository nd Archive, University of Zurich ZORA URL: Journl Article Accepted Version Originlly pulished t: Wilkens, Mirj R; Liesegng, Annette; Richter, Juli; Frser, Dvid R; Breves, Gerhrd; Schröder, Bernd (2014). Differences in periprtl plsm prmeters relted to clcium homeostsis of diry sheep nd gots in comprison with cows. Journl of Diry Reserch, 81(3): DOI:

2 Differences in periprtl plsm prmeters relted to clcium homeostsis of diry sheep nd gots in comprison with cows Mirj R. Wilkens *, Annette Liesegng,c, Juli Richter, Dvid R. Frser d, Gerhrd Breves, Bernd Schröder Deprtment of Physiology, University of Veterinry Medicine Hnnover, Foundtion, Hnnover, Germny Institute of Animl Nutrition, Vetsuisse Fculty Zurich, University of Zurich, Zurich, Switzerlnd c Center for Applied Biotechnology nd Moleculr Medicine, University of Zurich, Zurich, Switzerlnd d Fculty of Veterinry Science, University of Sydney, Sydney, Austrli * Corresponding uthor: Mirj R. Wilkens, Deprtment of Physiology, University of Veterinry Medicine Hnnover, Bischofsholer Dmm 15/102, Hnnover, Germny. Tel.: ; fx: E mil ddress: mirj.wilkens@tiho-hnnover.de Key words: trnsition; clcium homeostsis; close-up; dry period; ruminnts; one metolism; Short title: Periprtl clcium homeostsis in ruminnts

3 Summry: Recently it hs een demonstrted tht there re differences etween sheep nd gots in respect to the dpttion to clcium restricted diet. It ws the im of the present study to evlute whether species-specific peculirities lso occur when clcium homeostsis is chllenged y lcttion. Therefore, we investigted the time courses of plsm prmeters relted to clcium homeostsis (clcium, phosphte, clcitriol, the one resorption mrker CrossLps nd the one formtion mrker osteoclcin) during the trnsition period in multiprous nimls of oth species nd compred the results to dt from former study crried out with diry cows. Like in cows, plsm clcium nd the rtio of one formtion to one resorption decresed t prturition in gots while plsm clcitriol incresed. On the 10 th dy postprtum the one prmeters of gots reched preprtum vlues gin which ws not the cse in cows. Sheep were found to experience chllenge of clcium homeostsis lredy 10 dys efore prturition, reflected y very low rtio of one formtion to one resorption which ws not ccompnied y n increse in plsm clcitriol. Additionlly, sheep nd gots which hd een in milk for 3 months were smpled, dried-off nd smpled gin 6 weeks lter. In dried-off nimls there were no differences in prmeters of one metolism detectle. In conclusion we could show tht the contriution of one moilistion to the compenstion for the enhnced clcium demnd due to lcttion differs etween the three ruminnt species

4 Introduction Smll ruminnts re often used s models for cows to study sic spects of clcium (C) homeostsis. However, there re differences in homeosttic mechnisms etween gots nd sheep tht need to e considered efore ny results cn e extrpolted to diry cows, especilly with respect to the trnsition period. On ody weight sis the milk yield of diry gots is comprle to tht of diry cows nd hypoclcemi occurs in oth species usully t the onset of lcttion, while sheep develop hypoclcemi more often during lte gesttion (Oetzel, 1988). But when compring feeding ehviour, cttle nd sheep cn e regrded s grzers, while gots in their nturl hitt select high energy (concentrte) feed (Hofmnn, 1989). These differences in feed type might influence gstrointestinl minerl sorption s it hs een shown tht gots dpt more efficiently to dietry C restriction y up-regulting intestinl C trnsport thn sheep (Wilkens et l., 2011; Wilkens et l., 2012). Interestingly, it hs lso een reported tht reduction in C supply did not led to n increse in pprent digestiility of C in lctting cows (Tylor et l., 2008). Comprtive dt on the response of different ruminnt species to the chllenge of C homeosttic mechnisms t the onset of lcttion re limited. In studies investigting one metolism in gots nd sheep it hs een demonstrted tht round prturition sheep tend to hve greter concentrtions of one resorption mrkers nd more pronounced depression of one formtion mrkers in lood, compred to gots (Liesegng et l., 2006, 2007). As milk fever in diry cows is ssocited very closely with prturition, it ws the im of the present study to investigte chnges in plsm prmeters of C homeostsis during the periprtl period of sheep nd gots y tking smples in shorter intervls thn it hs een done in the studies mentioned ove nd compre them to respective dt from cows. Bsed on our former studies we hypothesise tht there re differences in the response to the periprtl chllenge of C homeostsis which cnnot e simply explined with the higher milk yield 72 usully oserved in gots nd cows. 3

5 Besides ionised nd totl C nd phosphte plsm, concentrtions of clcitriol, the iologiclly ctive metolite of vitmin D, were determined. Furthermore, the one mrkers were ddressed. Bone turnover or remodelling mens concurrent one formtion nd resorption (Allen, 2003). As solute vlues of iochemicl mrkers of one metolism re influenced y vrious fctors like ge, circdin rhythms nd seson (Hnnon & Estell, 2000), the rtio of osteoclcin to CrossLps ws used to ssess one turnover. The rtio of one formtion mrkers to one resorption mrkers hs een used efore to estimte the sttus of one remodelling in horses nd cows (Lepge et l., 1998; Liesegng et l., 2000) Mteril nd methods Animls, diets, milking pttern nd lood smpling The study ws crried out with 5 to 6 multiprous nimls of ech species (sheep, gots nd cows), ged etween 2 nd 5 yers. All nimls were of reeds used for milk production in Centrl Europe: Est Friesin diry sheep, Snen type gots nd Holstein-Friesin cows. Averge ody weights were 66.3 ± 1.6 kg (sheep), 49.1 ± 1.7 kg (gots) nd 679 ± 25 kg (cows). Sheep nd gots were housed in free-stll rn t the Deprtment of Physiology of the University of Veterinry Medicine, Foundtion, Hnover, Germny. During the entire oservtion period, the nimls hd ccess to hy (Tle 1), minerls nd wter d liitum. The nimls were group-fed preprtum, receiving 75 g concentrte (Tle 1) per 10 kg ody weight per dy. Immeditely fter prturition, the kids nd lms were removed nd milk yield ws recorded for 20 consecutive dys. The ewes nd does were milked nd provided with concentrte three times dily t 0800, 1400 nd 2000 h. The mount of concentrte ws clculted for ech individul niml ccording to the milk yield of the previous milking (800 g per kg milk) to meet the requirements for diry sheep nd gots recommended y the Society of Nutrition 98 Physiology (GfE). 4

6 Dt from cows were otined from previous study (Wilkens et l., 2012). The cows were kept on commercil diry frm locted in Sxony, Germny. They were fed totl mixed rtion d liitum efore nd fter prturition (C content.p.: 7.8 g/kg DM; C content p.p.: 10.0 g/kg DM). The clves were removed within 24 h postprtum, fter which milking ws done twice dily. In the present study, the periprtl plsm prmeters of 6 cows of the former control group were compred with respective vlues from the smll ruminnts. From clculted gesttionl dy 140 (sheep nd gots) or dy 175 (cows), two lood smples (lithium heprin nd EDTA) were collected from the jugulr (sheep nd gots) or coccygel vein (cows), every other dy t 0900 h until dy 10 postprtum. Additionl smples were tken immeditely fter prturition nd t 6, 12 nd 24 h postprtum. The preprtum smples were re-clssified ccording to the exct dy of prturition. Smples tken on dy 2 nd 1 preprtum were clssified s smple dy -2, smples tken on dy 4 nd 3 s smple dy -4, etc. A further 6 gots nd 5 sheep, of the sme ge nd reed were smpled fter three months of lcttion. They were then dried off nd smpled gin six weeks lter. The protocol of niml tretment ws pproved y the Animl Welfre Commissioner of the University of Veterinry Medicine, Foundtion, Hnover, Germny, nd its conduct ws supervised ccording to Germn Animl Welfre Lw Smple nlysis After mesuring ionised C in whole lood with lood gs nlyser (Chiron Dignostics, RpidL TM 348), smples were centrifuged (2,000 g, 15 min) t mient temperture nd plsm ws collected nd stored t -18 C. The concentrtions of phosphte nd totl C in plsm of sheep nd gots were mesured colorimetriclly y stndrd spectrometric techniques (Srkr & Chuhn, 1967; Kruse-Jrres, 1979), while totl C nd phosphte concentrtions in the plsm smples from cows were 5

7 determined y stndrd dignostic methods in the lortory of the Clinic for Cttle of the University of Veterinry Medicine, Foundtion, in Hnnover. Plsm clcitriol of sheep nd gots ws mesured with commercil rdioreceptor ssy (Immundignostik AG, Bensheim, Germny). Quntifiction of the one formtion mrker osteoclcin nd the one resorption mrker CrossLps ws done using commercil enzymelinked immunosorent ssy kits ccording to the mnufcturer s instructions (MicroVueTM Osteoclcin EIA Kit, Quidel Corportion, Snt Clr, USA; Serum CrossLps, IDS Ltd, Frnkfurt m Min, Germny) Dt presenttion nd sttisticl nlysis Dt re presented s men ± SEM. The dily milk yield of sheep nd gots is corrected for the nimls ody weights. All sttisticl nlyses were performed using GrphPd Prism 5.0 (GrphPd Softwre, Sn Diego, USA). Gussin distriution ccording to Kolmogorov-Smirnov ws confirmed for ll dt. Comprison of periprtl ionised nd totl C, phosphte, CrossLps nd osteoclcin plsm concentrtions ws crried out y nlysis of vrince (ANOVA) for repeted mesurements with sturted model of the fixed fctor species. Bonferroni post-test ws pplied to revel species differences t ech time point nd differences over time within ech species. In ll cses, P vlues < 0.05 were considered sttisticlly significnt Results Milk yield Three of the 5 ewes nd 5 of the 6 does produced twins, while the remining smll ruminnts nd ll the cows hd single offspring. Milk yield ws not ffected y the numer of offspring. There ws no significnt difference in milk yield etween the sheep nd gots over the first few 6

8 dys fter prturition. However, dily milk production of the gots then incresed to mximum of l/kg BW, wheres milk yield of the ewes remined more or less constnt t level of 0.04 l/kg BW per dy (Fig. 1) Mcro minerls in lood nd plsm Whole lood nd plsm concentrtions of ionised nd totl C nd phosphte mesured in sheep, gots nd cows round prturition re given in Figures 2, 3 nd 4. Compred to dy 2 preprtum, ionised C mesured in whole lood of gots showed significnt decrese t prturition nd lso on the 10 th dy postprtum. There ws no similr chnge in ionised C ssocited with lming in ewes. The trnsient decrese oserved in cows with minimum t 12 hours postprtum ws not sttisticlly significnt ecuse of high individul vrinces, ut compred to sheep nd gots postprtum ionised C in cows ws significntly lower. However, the gret chllenge of C homeostsis in cows t prturition ecomes ovious when the plsm concentrtions of totl C re considered. In ll species, smll, ut not sttisticlly significnt decrese in plsm phosphte ws oserved t prturition. Intriguingly, pronounced increse in plsm phosphte ws found on the 10 th dy postprtum in gots Clcitriol The profile of plsm concentrtions showed tht in gots, clcitriol ws highest t prturition while sheep hd no significnt chnges nd cows showed the highest clcitriol levels on the 2 nd dy postprtum (Fig. 5) Mrkers of one formtion nd resorption 7

9 The rtio of the one formtion mrker osteoclcin to the one resorption mrker CrossLps is given in Figure 6. In sheep plsm, very low rtio ws found throughout the entire oservtion period, while gots nd cows hd significntly greter rtios during the lst gesttionl dys which then decresed t prturition. On the 10 th dy postprtum sl vlues were found gin in gots, while the cows osteoclcin to Crosslps rtios remined s low s those of sheep Effects of terminting lcttion Comprisons of plsm concentrtions of totl C, phosphte, clcitriol nd the rtio of osteoclcin to CrossLps in ewes nd does fter three months of lcttion nd six weeks fter the end of lcttion re presented in Tle 2. Plsm concentrtions of totl C were not ffected y lcttion sttus. However, lower concentrtions were found in oth groups of sheep compred to gots. Both species showed smll increse in plsm phosphte fter lcttion hd cesed. While no effects of lcttion sttus were found with clcitriol concentrtions, the rtio of osteoclcin to CrossLps incresed mrkedly in oth species fter lcttion hd cesed. In contrst to periprtl vlues, there were no species differences in these one mrker rtios in non-lctting nimls Discussion There is sudden increse in the outflow of C from lood t the onset of lcttion compred to the lst dys of gesttion (Horst et l., 2005). The resulting trnsient decrese in plsm C t prturition nd shortly fter hs een descried for cows in numerous studies (Reinhrdt et l., 2011). The discrepncy etween ionised nd totl C in cows fter prturition in the present study could e explined y fctors cused y the negtive energy lnce lmost lwys reported for cows in erly lcttion (Butler & Smith, 1989). For exmple, ltertions of plsm lumin 8

10 or ph might hve ffected the rtio etween ionised nd totl C. In contrst to the group fed diry cows, the smll ruminnts were feed individully ccording to their milk yield. The sence of such depression of C t prturition in sheep hs lredy een reported (Liesegng, 2008). This might suggest tht in contrst to gots nd cows there is no prticulr chllenge to the mechnisms of C homeostsis t lming due to the secretion of C in milk. However, s there were only minor differences in milk production etween sheep nd gots immeditely fter prturition, it is unlikely tht the C demnd for milk production during the first 24 hours p.p. ws very much higher in gots compred to sheep. The dily plcentl trnsfer in ewes etween dy 133 nd 140 of gesttion hs een shown to mount for 255 mg per kg foetl ody weight (Durnd et l., 1983). Assuming C concentrtion of 2.5 g/l in colostrum (Liesegng 2008), for the sheep in the present study the loss of C into the milk hs een pproximtely 4 g on the first dy p.p. compred to n estimted dily demnd of 2 g for lte gesttion. But in contrst to does nd cows, the osteoclcin to CrossLps rtio in ewes ws lredy very low t the end of gesttion. Since in non-lctting nimls there were no differences etween gots nd sheep, this low formtion to resorption mrker rtio is most proly not chrcteristic for sheep in generl nor cused y vritions in the sensitivities of the ELISA kits. The time course of the osteoclcin to CrossLps rtio round prturition more proly suggests tht in ewes the C homeosttic mechnisms hve lredy een chllenged efore lming nd there my hve een greter contriution of the skeleton to mintennce of C homeostsis thn in the other two ruminnt species. This is in line with the clinicl oservtion tht ewes often develop hypoclcemi during the lst dys efore lming when the foetl skeleton is minerlised (Oetzel, 1988) nd tht the periprtl plsm C concentrtions re lower in twin-ering thn in single-ering ewes (Roofi et l., 2013). However, ll of the gots except one in the present study lso produced twins. As it hs lredy een demonstrted tht gots hve greter ility to dpt to dietry C restriction thn sheep 9

11 (Wilkens et l., 2012), it my e tht the does were dpted etter thn sheep to the enhnced C demnd of foetl one growth in lte pregnncy. The onset of lcttion induced smll decrese in ionised C ccompnied y concurrent increse in clcitriol in does. A decrese in ionised C leds to secretion of prthyroid hormone (PTH) which thn stimultes the renl 1α-hydroxylse, the enzyme needed for the trnsformtion of 25-hydroxyvitmin D to 1,25- dihydroxyvitmin D, the ctive hormone clcitriol (Frser & Kodicek, 1970). Assuming tht C homeostsis in ewes hd lredy een severely chllenged efore prturition, one would expect clcitriol response occurring even erlier in these nimls. However, this ws not the cse. Lower clcitriol concentrtions in sheep compred to gots experiencing the sme dietry C restriction hve lredy een demonstrted (Wilkens et l., 2010; Wilkens et l., 2012). As there is no suitle ssy ville for the determintion of PTH in smll ruminnt species, it is difficult to revel the resons for this phenomenon. In cows nd gots one resorption seemed to e induced not efore prturition. But while gots reched pre-kidding vlues t the 10 th dy postprtum gin, cows nd sheep s osteoclcin to CrossLps rtios remined very low. This might point to re more rpid stimultion of gstrointestinl C sorption in gots llowing the nimls do reduce one moilistion gin. For sheep it hs een shown tht the mximl efficiency of gstrointestinl C sorption ws reched 2 months fter prturition, lthough one resorption hd lredy een stimulted efore lming (Brithwite et l., 1970). Comprle lnce studies crried out with gots re not ville. In cows significnt increse of gstrointestinl C sorption ws found to tke plce one week postprtum (vn t Klooster, 1976) or etween the 10 th nd the 20 th dy fter prturition, respectively (Rmerg et l., 1970). It should e tken into ccount tht these dt were otined some time go when milk production in diry cows ws not s high s nowdys. Aginst the ckground of the low osteoclcin to CrossLps rtios found in cows on the 10 th dy postprtum it might e speculted tht one moilistion ws more prolonged in cows of 252 the present study. 10

12 The reson for the slight decrese in plsm phosphte oserved in ll species is usully ssumed to represent loss of phosphte to the milk (Roertson et l., 1956). Furthermore, it hs een shown tht decrese in plsm C induces concurrent increse in cortisol. Cortisol ws demonstrted to hve n impct on plsm phosphte (Horst & Jorgensen, 1982). No stisfying explntion could e found for the increse in gots plsm phosphte concentrtions on the 10 th dy postprtum. As the lood concentrtion of ionised C showed second decrese on the 10 th dy, too, these ltertions might e ssocited with the steep rise in milk production oserved in does etween the 7 th nd the 12 th dy fter prturition. The role of phosphte in lctting nimls is not yet fully understood. In contrst to clcium, plsm concentrtions of phosphte re not tht strictly controlled nd the exchnge etween the different pools is more complicted. Phosphte is not only moilised from one, ut lso from soft tissues nd in ruminnts lrge mounts of phosphte secreted vi the slivry glnds nd resored gin in the gstrointestinl trct hve to e tken into ccount (Brithwite, 1983). However, the effect of drying-off on plsm phosphte underlines tht it might e influenced y the hormonl regultion mechnisms involved in lcttion nd one metolism Conclusion We could demonstrte tht in line with former studies sheep seem not to respond with n dequte stimultion of clcitriol synthesis to chllenges of C homeostsis. Furthermore, striking differences regrding periprtl one metolism were oserved etween the three ruminnt species investigted. To evlute whether sheep or gots re the etter model for studying C homeostsis in the diry cow, further studies under more controlled feeding regimes of the cows nd lrger numer of nimls re needed The finncil support of the Deutsche Forschungsgemeinschft (SCHR 342/8-2) is grtefully 278 cknowledged. 11

13 279 12

14 280 Tles Tle Ingredients of hy nd concentrte fed to sheep nd gots expressed s percentge of originl sustnce; n.d.: not detectle using stndrd procedures. 286 Hy Concentrte Crude protein Crude ft Crude fire Crude sh Clcium Phosphorus Sodium Energy [MJ per kg] Vitmin D [IU/kg] n.d. 1,

15 289 Tle Totl clcium (mmol/l), phosphte (mmol/l), clcitriol (pg/ml) nd the rtion etween osteoclcin (ng/ml) nd Crosslps (ng/ml) in plsm of gots nd sheep mesured fter 3 months in milk nd 6 weeks fter hving een dried-off, respectively. Results of 2wy ANOVA (species, effect of lcttion nd interction). Mens ± SEM. 295 Totl clcium Phosphte Clcitriol Rtio osteoclcin to CrossLps Gots Lctting (6) 2.56 ± ± ± ± 5.8 Dried-off (6) 2.63 ± ± ± ± 5.2 Sheep Lctting (5) 2.20 ± ± ± ± 5.3 Dried-off (5) 2.18 ± ± ± ± 12 ANOVA Species P < n.s. n.s. n.s. Lcttion n.s. P < 0.05 n.s. P < 0.05 Interction n.s. n.s. n.s. n.s

16 297 Figures Figure 1 Dily milk yield of gots nd sheep normlised to the nimls ody weight. RM ANOVA reveled significnt effects of time (P < 0.001), species (P < 0.001) nd n interction of time nd species (P < 0.001). Significnt differences etween species reveled y Bonferroni posttest for ech dy re mrked with sterisks (P < 0.05: *; P < 0.01: **; P < 0.001: ***). Mens ± SEM Figure 2 Blood concentrtions of ionised clcium mesured in gots, sheep nd cows round prturition. RM ANOVA reveled significnt effects of species (P < 0.01) nd n interction of time nd species (P < 0.05). Different letters represent significnt differences within one species. The symols # nd $ indicte significnt differences etween cows nd gots (#) or sheep ($), respectively. Mens ± SEM Figure 3 Plsm concentrtions of totl clcium mesured in gots, sheep nd cows round prturition. RM ANOVA reveled significnt effects of time (P < 0.001) nd species (P < 0.001). Different letters represent significnt differences within one species. The symols # nd $ indicte significnt differences etween cows nd gots (#) or sheep ($), respectively. Mens ± SEM Figure 4 Plsm concentrtions of phosphte mesured in gots, sheep nd cows round prturition. RM ANOVA reveled significnt effects of time (P < 0.001) nd n interction of time nd species 15

17 (P < 0.001). Different letters represent significnt differences within one species. The symols # nd indicte significnt differences etween gots nd cows (#) or sheep ( ), respectively. Mens ± SEM Figure 5 Plsm concentrtions of clcitriol mesured in gots nd sheep round prturition. RM ANOVA reveled significnt effects of time (P < 0.05) nd species (P < 0.05). Different letters represent significnt differences within one species. Mens ± SEM Figure 6 Rtio etween plsm concentrtions of osteoclcin nd CrossLps mesured in gots, sheep nd cows round prturition. RM ANOVA reveled significnt effects of time (P < 0.001), species (P < 0.001) nd n interction of time nd species (P < 0.001). Different letters represent significnt differences within one species. The symols #, $ nd indicte significnt differences etween gots nd cows (#), sheep nd cows ($) or sheep nd gots ( ), respectively. Mens ± SEM

18 References Allen MJ 2003 Biochemicl mrkers of one metolism in nimls: uses nd limittions. Veterinry Clinicl Pthology Brithwite GD, Glscock RF & Rizuddin S 1970 Clcium metolism in pregnnt ewes. British Journl of Nutrition Brithwite GD 1983 Clcium nd phosphorus requirements of the ewe during pregnncy nd lcttion. British Journl of Nutrition Butler WR & Smith RD 1989 Interreltionships etween energy lnce nd postprtum reproductive function in diry cttle. Journl of Diry Science Durnd D, Brithwite GD & Brlet JP 1983 The effect of 1 lph-hydroxycholeclciferol on the plcentl trnsfer of clcium nd phosphte in sheep. British Journl of Nutrition Frser DR & Kodicek E 1970 Unique iosynthesis y kidney of iologicl ctive vitmin D metolite. Nture Hnnon R & Estell R 2000 Prenlyticl vriility of iochemicl mrkers of one turnover. Osteoporosis Interntionl 11 S30-44 Hofmnn RR 1989 Evolutionry steps of ecophysiologicl dpttion nd diversifiction of ruminnts: comprtive view of their digestive systems. Oecologi Horst RL, Goff JP & Reinhrdt TA 2005 Adpting to the trnsition etween gesttion nd lcttion: differences etween rt humn nd diry cow. Journl of Mmmry Glnd Biology nd Neoplsi Horst RL & Jorgensen NA 1982 Elevted plsm cortisol during induced nd spontneous hypoclcemi in ruminnts. Journl of Diry Science Kruse-Jrres JD 1979 Klinische Chemie Vol II: Spezielle klinisch-chemische Anlytik, Fischer, Stuttgrt Germny 17

19 Lepge OM, Hrtmnn DJ, Eicher R, Ueelhrt B, Tschudi P & Ueelhrt D 1998 Biochemicl mrkers of one metolism in drught nd wrmlood horses. The Veterinry Journl Liesegng A 2008 Influence of nionic slts on one metolism in periprturient diry gots nd sheep. Journl of Diry Science Liesegng A, Eicher R, Sssi ML, Risteli J, Krenzlin M, Riond JL & Wnner M 2000 Biochemicl mrkers of one formtion nd resorption round prturition nd during lcttion in diry cows with high nd low stndrd milk yields. Journl of Diry Science Liesegng A, Risteli J & Wnner M 2006 The effects of first gesttion nd lcttion on one metolism in diry gots nd milk sheep. Bone Liesegng A, Risteli J & Wnner M 2007 Bone metolism of milk gots nd sheep during second pregnncy nd lcttion in comprison to first lcttion. Journl of Animl Physiology nd Animl Nutrition Oetzel GR 1988 Prturient presis nd hypoclcemi in ruminnt livestock. Veterinry Clinics of North Americ: Food Animl Prctice Rmerg CF, Myer GP, Kronfeld DS, Phng JM & Bermn M 1970 Clcium kinetics in cows during lte pregnncy prturition nd erly lcttion. Americn Journl of Physiology Roofi A, Jfrin M, Sfi S & Vtnkhh M 2013 Fluctutions in energy-relted metolites during the peri-prturient period in Lori-Bkhtiri ewes. Smll Ruminnt Reserch Reinhrdt TA, Lippolis JD, McCluskey BJ, Goff JP & Horst RL 2011 Prevlence of suclinicl hypoclcemi in diry herds. The Veterinry Journl Roertson A, Mrr A & Moodie EW 1956 Milk fever. Veterinry Record

20 Srkr BC & Chuhn UP 1967 A new method for determining micro quntities of clcium in iologicl mterils. Anlyticl Biochemistry Tylor MS, Knowlton KF, McGillird ML, Seymour WM & Herein JH 2008 Blood minerl hormone nd osteoclcin responses of multiprous Jersey cows to n orl dose of 25- hydroxyvitmin D3 or vitmin D3 efore prturition. Journl of Diry Science Vn t Klooster AT 1976 Adption of clcium sorption from the smll intestine of diry cows to chnges in the dietry clcium intke nd t the onset of lcttion. Zeitschrift fuer Tierphysiologie, Tierernehrung und Futtermittelkunde Wilkens MR, Mrochen N, Breves G & Schroder B 2010 Effects of 125-dihydroxyvitmin D3 on clcium nd phosphorus homeostsis in sheep fed diets either dequte or restricted in clcium content. Domestic Animl Endocrinology Wilkens MR, Mrochen N, Breves G & Schroder B 2011 Gstrointestinl clcium sorption in sheep is mostly insensitive to n limentry induced chllenge of clcium homeostsis. Comprtive Biochemistry nd Physiology Prt B: Biochemistry nd Moleculr Biology Wilkens MR, Oerheide I, Schroder B, Azem E, Steinerg W & Breves G 2012 Influence of the comintion of 25-hydroxyvitmin D3 nd diet negtive in ction-nion difference on periprtl clcium homeostsis of diry cows. Journl of Diry Science Wilkens MR, Richter J, Frser DR, Liesegng A, Breves G & Schröder B 2012 In contrst to sheep gots dpt to dietry clcium restriction y incresing intestinl sorption of clcium. Comprtive Biochemistry nd Physiology Prt A: Moleculr nd Integrtive Physiology

21 Milk yield in L per kg ody weight nd dy 0.10 *** * ** Dys fter prturition Gots (6) Sheep (5) Fig. 1

22 C 2+ in mmol/l $ # dys.p. 2 dys.p. t prturition 6 hours p.p. 12 hours p.p. 1 dy p.p. 2 dys p.p. 10 dys p.p. Gots (6) Sheep (5) Cows (6) Fig. 2

23 C t in mmol/l $ # c # $ # # c c c # # c c dys.p. 2 dys.p. t prturition 6 hours p.p. 12 hours p.p. 1 dy p.p. 2 dys p.p. 10 dys p.p. Gots (6) Sheep (5) Cows (6) Fig. 3

24 P i in mmol/l # dys.p. 2 dys.p. t prturition 6 hours p.p. 12 hours p.p. 1 dy p.p. 2 dys p.p. 10 dys p.p. Gots (6) Sheep (5) Cows (6) Fig. 4

25 Clcitriol in pg/ml, gots nd sheep dys.p. 2 dys.p. t prturition 12 hours p.p. 2 dys p.p. 10 dys p.p. Gots (6) Sheep (5) Fig. 5

26 Rtio osteoclcin to CrossLps $ $ # 20 c c c c c 0 10 dys.p. 2 dys.p. t prturition 6 hours p.p. 12 hours p.p. 1 dy p.p. 2 dys p.p. 10 dys p.p. Gots (6) Sheep (5) Cows (6) Fig. 6