Osteoporosis after heart transplantation with reference to immunosuppression and renal function

Abstract

Abstract Background Osteoporosis is commonly found in heart transplantation (HT) recipients, and may develop as an adverse effect of the immunosuppressive therapy, as well as be a consequence of factors associated with heart failure prior to HT. Chronic kidney disease (CKD) is furthermore, like osteoporosis, frequently found in the HT patient population, and may also arise as a side-effect of the immunosuppressive therapy. Aims and method We sought to describe the bone mineral density (BMD) evolution, predictors of osteoporosis, and survival, as well as incidence of osteoporosis in relation to CKD up to 10 years after HT. The project was conducted as a retrospective cohort study including patients who underwent HT at an age of at least 20 years between January 1988 and June 2016 at our center. The project was approved by the local ethics board (approval nos. 2010/114, 2011/777, 2014/92). Results Pre-transplant BMD was a negative predictor of osteoporosis during the first post-operative year, with a HR of 0.13 (95% CI 0.063; 0.26; P<0.001) and 0.54 (95% CI 0.34; 0.85; P<0.001) in the lumbar spine and femoral neck, respectively, adjusted for age, gender, BMI, and immunosuppressive therapy. Similarly, pre-transplant BMD was a negative predictor of osteoporosis also up to 10 years after HT, with a HR of 0.19 (95% CI 0.11; 0.32; P<0.001) and 0.55 (95% CI 0.39; 0.78; P=0.001), in the lumbar spine and femoral neck, respectively, adjusted for age, gender, BMI, and immunosuppressive therapy. CKD stage 3 or worse before HT was associated with a greater gain in BMD after HT compared with CKD stage less than 3 or normal kidney function (−2.5% [−5.6; 0.6] versus −6.6% [−8.8;-4.5], P=0.029), and was not associated with osteoporosis (Figure 1). Also, the cumulative incidence of osteoporosis in the lumbar spine after HT was higher in the group with CKD stage less than 3 or normal kidney function. Conclusions The greatest drop in BMD occurs within the first year after HT. Short- and long-term incidence of osteoporosis is positively associated with pre-transplant bone strength, suggesting that early initiation of osteoporosis preventive treatment, pharmacologically and non-pharmacologically, may be beneficial in preventing long- and short-term fracture-related morbidity and morbidity after HT. Moreover, CKD stage 3 or worse before HT was associated with higher lumbar BMD after HT, and was not a predictor of osteoporosis. CKD stage less than 3 or normal kidney function before HT exhibited a greater BMD loss in the lumbar spine. Finally, the change in GFR during the first postoperative year was not associated with long-term BMD loss or osteoporosis. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Anna-Lisa & Sven-Erik Lundgren's Foundation and ALF's Foundations, Lund, Sweden Figure 1