Bone turnover markers in medicamentous and physiological hyperprolactinemia in female rats

Abstract

Background/Aim. There is a lack of data on the effects of prolactin on calcium metabolism and bone turnover in hyperprolactinemia of various origins. The aim of this study was to compare the influence of medicamentous and physiological hyperprolactinemia on bone turnover in female rats. Methods. Experimental animals (18 weeks old, Wistar female rats) were divided as follows: the group P - 9 rats, 3 weeks pregnant; the group M3-10 rats that were intramuscularly administrated sulpirid (10 mg/kg) twice daily for 3 weeks, the group M6 - 10 rats that were intramuscularly administrated with sulpirid (10 mg/kg) twice daily for 6 weeks, and age matched nulliparous rats as the control group: 10 rats, 18-week-old (C1) and 7 rats, 24 weeks old (C2). Laboratory investigations included serum ionized calcium and phosphorus, urinary calcium and phosphorous excretion, osteocalcin and serum procollagen type 1 N-terminal propeptide (P1NP). Results. Experimental animals in the group P compared to the control group, displayed lower mean serum ionized calcium (0.5 ? 0.2 vs 1.12 ? 0.04 mmol/L; p < 0.001); higher mean serum phosphorus (2.42 ? 0.46 vs 2.05 ? 0.2 mmol/L; p < 0.05); increased urinary calcium (3.90 ? 0.46 vs 3.05 ? 0.58; p < 0.01) and significantly increased P1NP (489,22 ? 46,77 vs 361.9 ? 53,01 pg/mL; p < 0.001). Experimental animals in the group M3 had significantly decreased P1NP, compared to the control group. Prolongated medicamentous hyperprolactinemia (the group M6) induced increased serum ionized calcium (1.21 ? 0.03 vs 1.15 ? 0.02 mmol/L; p < 0.001); decreased serum phosphorus (1.70 ? 0.13 vs 1.89 ? 0.32 mmol/L; p < 0.001); decreased osteocalcin and P1NP. Conclusions. Physiological hyperprolactinemia does not have such harmful effect on bone metabolism as medicamentous hyperprolactinemia. Chronic medicamentous hyperprolactinemia produces lower serum levels of bone formation markers. Assessment of bone turnover markers in prolongated medicamentous hyperprolactinemia provides an opportunity for earlier diagnosis of bone metabolism disturbances and should be considered as mandatory.Uvod/Cilj. Nema dovoljno podataka o efektima prolaktina na metabolizam kalcijuma i kostani promet kod hiperprolaktinemije razlicitog porekla. Cilj ovog rada bio je da uporedi uticaj medikamentne i fizioloske hiperprolaktinemije na kostani metabolizam kod zenki pacova. Metode. Eksperimentalne zivotinje (zenke pacova soja Wistar, stare 18 nedelja) podeljene su na sledece grupe: grupa P - devet pacova u trecoj nedelji trudnoce; grupa M3 - 10 pacova, kojima je tokom tri nedelje, dva puta dnevno, davan intramuskularno sulpirid (10 mg/kg); grupa M6 - 10 pacova kojima je tokom sest nedelja, davan sulpirid (10 mg/kg) intramuskularno, dva puta dnevno; starosno odgovarajuce nulipare zenke pacova kao kontrolne grupe: C1 - 10 pacova, starih 18 nedelja i C2 - sedam pacova, starih 24 nedelje. Odredjivana je koncentracija jonizovanog kalcijuma i fosfora u serumu, 24-casovno izlucivanje kalcijuma i fosfora urinom, osteokalcin i serumski amino terminalni propeptid prokolagena tipa I (P1NP). Rezultati. U poredjenju sa kontrolnom grupom eksperimentalne zivotinje u grupi P imale su snizen jonizovan kalcijum u serumu (0,5 ? 0,2 vs 1,12 ? 0,04 mmol/L; p < 0,001), povisene fosfate u serumu (2,42 ? 0,46 vs 2,05 ? 0,2mmol/L; p < 0,05), povecano 24-casovno izlucivanje kalcijuma urinom (3,90 ? 0,46 vs 3,05 ? 0,58 mmol/24 h; p < 0,01) i znacajno povisen P1NP (489,22 ? 46,77 vs 361,9 ? 53,01 pg/mL; p < 0,001). Znacajan pad P1NP zabelezen je u eksperimentalnoj grupi M3 u poredjenju sa kontrolnom grupom. Prolongirana medikamentna hiperprolaktinemija u grupi M6 dovela je do porasta jonizovanog kalcijuma u serumu (1,21 ? 0,03 vs 1,15 ? 0,02mmol/L; p < 0,001), pada fosfata (1,70 ? 0,13 vs 1,89 ? 0,32 mmol/L; p < 0,001) i snizenja koncentracije osteokalcina i P1NP. Zakljucak. Fizioloska hiperprolaktinemija u manjoj meri utice na kostani metabolizam nego medikamentna hiperprolaktinemija. Hronicna medikamentna hiperprolaktinemija dovodi do pada koncentracije P1NP, sto je odraz snizene kostane formacije. Rutinsko odredjivanje biohemijskih markera kostanog metabolizma u prolongiranoj medikamentnoj hiperprolaktinemiji pruza mogucnost ranije dijagnoze poremecaja kostanog metabolizma.