Background: Endocrine disturbances are important complications post heart transplant (HT). Most dynamic changes in endocrine system occur in the first year, also increased bone turnover and rapid mineral bone density (BMD) reduction. Treatment with methylprednisolone has the largest effect on BMD. According to preclinical and animal studies also other immunosuppressives have deleterious effects on bone. With measurement of bone turnover markers (BTM) and BMD, we do not recognize all patients at risk of fracture. FRAX calculator is not suitable for this specific population. Microarchitecture is important factor in bone strength. We can assess it with trabecular bone score (TBS). TBS is an index which is acquired from dual energy X-ray absorptiometry and indirectly estimates trabecular microarchitecture. TBS independently from measurement of BMD identifies patients at risk of fractures in different populations, such as postmenopausal and glucocorticoid induced osteoporosis, in diabetes mellitus (DM) type 1 or type 2 and after kidney transplant. Until now there was not investigated incidence of all possible endocrine disturbances post HT, effect of immunosuppressives on BTM’s, BMD, efficiency of treatment with zoledronic acid (ZA) and role of TBS in patients post HT.
Methods: We set up a three-part survey. In first retrospective part we examined prevalence of different endocrine abnormalities and their coincidence in 123 patients in first year post HT. In second part we conducted cross-sectional study on 123 patients less than 9 months post HT, with longitudinal follow-up 6-12 months after first outpatient visit. We investigated differences in effect of immunosuppressive protocols cyclosporine A/mycophenolic acid (CsA/MA) and tacrolimus/mycophenolic acid (T/MA) on BMD and BTM C-terminal telopeptide (CTX) as a reference marker of bone resorption and procollagen type 1 N-terminal propeptide (PINP) as a reference marker of bone formation and the effect of treatment with ZA. In third part we conducted cross-sectional study on 87 patients. We assessed BMD, TBS and in part of cohort also X-ray of the spine.
Results: Osteopenia was present in 59 (48,0%), osteoporosis in 26 (21,1%), at least 1 osteoporotic fracture in 21 (17.1%) patients. Deficiency or insufficiency of 25-OH-vitamin D (25OHD) was present in 64 (54,7%) patients, secondary hyperparathyroidism in 19 (17,3%), new onset diabetes after transplantation (NODAT) or DM type 2 39 (31,7%) and thyroid dysfunction in 15 (13,9%). Most patients had 2 do 3 endocrine disturbances, only 4,1% did not have any endocrine disturbances. Group T/MK, had higher PINP (p < 0,001) and lower CTX (p < 0,001) on control visit. No differences in BTM were present in group CsA/MK between first and control visit (PINP p = 0,114 and CTX p = 0,433). Group T/MK treated with ZA, had reduced BTM (CTX p < 0,001 and PINP p < 0,001) in regard to patients who did not receive ZA. In group CsA/MK there were no differences between group treated with ZA and which did not receive ZA (CTX p = 0,573 and PINP p = 0,635). Degraded or partially degraded TBS had 48 (55,2%) and reduced BMD 46 (52,9%). The greatest number of fractures occurred in group with osteopenia (9 fractures) and partially degraded TBS (9 fractures). According to area under the ROC curve none of the parameters predicted presence of fractures (all parameters p > 0.05). There was negative correlation between TBS and BMI (Spearman's Rho ⠒0,508; p < 0,001). The lowest TBS was in group between 3- and 5-years post HT (1.249 (IQR 1.172⠒1.292)). In group more than 5 years post HT TBS (1.341 (IQR 1.228⠒1.382)) was comparable to group immediately post HT (1.346 (IQR 1.257⠒1.413)).
Conclusions: In retrospective part of study, we found that in early period post HT, most prevalent endocrine disorders were low 25OHD, low BMD and hypogonadism in men. Most patients had multiple endocrine disorders. In second part we found that patients receiving T/MA had an increase of PINP and decrease of CTX on follow-up. When treated with ZA both BTM decreased. There were no differences in group receiving CsA/MA. In third part we found that TBS in comparison with BMD does not improve prediction of osteoporotic fracture. Number of patients with degraded TBS and low BMD are comparable. TBS was dependent of time from HT and was not BMD.
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