High Prevalence of Low Bone Turnover and Occurrence of Osteomalacia after Kidney Transplantation

Abstract

Abstract. Kidney transplantation corrects most of the metabolic abnormalities that cause renal osteodystrophy. However, many transplanted patients develop osteoporosis and other bone lesions that are related, at least in part, to their immunosuppressive regimen. The precise histologic patterns of bone disease after transplantation are not well defined. In a study designed to investigate this issue, 57 adult posttransplant patients agreed to undergo bone biopsies and blood drawings. There were 32 men and 25 women, mean age 45 ± 2 yr, who had received a kidney transplantation 5.6 ± 0.8 yr before biopsy. History of bone pain, fractures, and avascular necrosis was found in 22, 12, and 7 patients, respectively. Serum creatinine was 1.68 ± 0.1 mg/dl, 21% of patients were hypercalcemic, 63.2% had elevated parathyroid hormone (PTH) (>65 pg/ml), and 91.2% had normal calcitriol levels. Cancellous bone volume/tissue volume was below normal compared to age- and gender-matched control subjects in 56.1% of patients. Bone turnover (activation frequency) was low in 45.6%, normal in 28.1%, and elevated in 26.3% of patients. Bone formation rate/bone surface was low in 59.7%, normal in 35%, and elevated in 5.3% of the patients. Erosion surface/bone surface was high in 21.1% of patients. Mineralization was prolonged in 87.5% of patients, including 9 patients with osteomalacia and 12 patients with focal osteomalacia. Cumulative and maintenance doses of prednisone and time elapsed since transplantation correlated negatively with bone volume and bone turnover (r= -0.32 to -0.59,P< 0.05 to 0.01), whereas cumulative doses of cyclosporine or azathioprine, age, gender, or serum PTH levels did not. Regression analysis identified prednisone as the main factor responsible for low bone volume and bone turnover (r= 0.54 andr= 0.43,P< 0.01). No factors were found to predict delayed mineralization. The present study shows that low bone volume, low bone turnover, and generalized or focal osteomalacia are frequent histologic features in transplanted patients. The effects of age, gender, PTH, and cyclosporine on bone volume and bone turnover are apparently overridden by the prominent effects of glucocorticoids. The prevalence of mineralization defect in the presence of normal serum levels of calcidiol and calcitriol suggests vitamin D resistance and deserves further study.

Contemporary kidney transplantation has a limited impact on bone microarchitecture

“…While earlier studies reported substantial bone loss in the first year post-transplantation ( Julian et al, 1991 ; Heaf, 2003 ), stability of trabecular bone mass is a consistent finding in contemporary kidney transplant recipients ( Iyer et al, 2014 ; Evenepoel et al, 2020 ; Evenepoel et al, 2017 ; Marques et al, 2019 ). As several studies demonstrated a relationship between cumulative steroid dose and post-transplantation bone loss ( Evenepoel et al, 2017 ; Monier-Faugere et al, 2000 ; Parker et al, 1999 ; Rojas et al, 2003 ), the introduction of steroid minimization protocols has been proposed as an explanation for this beneficial trend ( Iyer et al, 2014 ; Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group, 2017 ).…”

Prevalence of Musculoskeletal Manifestations in Adult Kidney Transplant’s Recipients: A Systematic Review

“…The effects of age, gender, PTH, and CyA on bone volume and bone turnover were ignored by the prominent effects of glucocorticoids. The prevalence of mineralization defect in the presence of normal serum levels of calcidiol and calcitriol suggests vitamin D resistance [ 42 ]. Ulivieri F, et al, 2002 showed that in twenty KTx male patients received one of two regimens (CyA combined with methylprednisolone with or without azathioprine).…”

“…Many other studies revealed that the risk factors involved low BMD post-KTx include increasing age, time after transplant, gender, and ethnicity [ 71 , 72 , 73 , 74 ]. Another study showed that the effects of age, gender, PTH, and CyA on bone density and bone turnover are masked by the prominent effects of steroids [ 42 ]. However, Aroldi and colleagues investigated the effects of immunosuppressive regimens on vertebral BMD in KTxR and revealed that the lumbar BMD decreased significantly in KTxR given CyA with steroids compared to those under CyA alone [ 75 ].…”

Bone and Mineral Disorder in Renal Transplant Patients: Overview of Pathology, Clinical, and Therapeutic Aspects

“…Regarding osteoporosis, the use of GCs remains the key risk factor for the development of this type of bone disease. An early post-RTx time is characterised by a rapid loss of bone mass that mainly affects trabecular bone due to intensive GC regimens ( 44 ). The GCs inhibit osteoblast proliferation and differentiation and stimulate apoptosis of both osteoblasts and osteoclasts.…”