Evolution of Bone Density, Bone Micro-architecture and Vascular Calcifications in Patients After Kidney Transplantation

Bone and mineral abnormalities are frequent in kidney transplant patients and are associated with a high risk of fracture, cardiovascular mortality, but also with an increase in the frequency of hospitalisations and thus healthcare's costs. The pathophysiology of bone disorders appearing after transplantation arises from a complex interaction between different factors. These include both pre-transplant renal osteodystrophy lesions and bone loss associated with the kidney transplant itself. This bone loss results from a variety of causes. The management of these bone abnormalities is complex in daily clinical practice because only the bone biopsy can accurately determine the type of abnormality present, and this examination is rarely performed due to its invasive nature. The link between the development of bone abnormalities and the presence or even the progression of vascular calcifications remains very poorly understood. This link is however fundamental because vascular calcifications could explain the increased risk of cardiovascular mortality in these patients. Understanding and diagnosing bone abnormalities early, ideally in a non-invasive manner, could help prevent bone and vascular degradation frequently found after renal transplantation.

Despite significant improvement in recent years, mortality as well as cardiovascular morbidity remain very high in kidney transplant patients. The reported annual risk of fatal or non-fatal cardiovascular events is 3.5% to 5%, even after adjusting for traditional risk factors (such as diabetes, hypertension, obesity, smoking and dyslipidemia). Certain factors related to chronic kidney disease (CKD) or transplant appear to influence the high incidence of cardiovascular events. These include, among others, the duration of dialysis before the transplant, the function of the graft after transplantation, proteinuria, episodes of acute rejection, new cases of post-transplant diabetes, the toxic effects of immunosuppressive drugs but also the bone metabolism abnormalities observed in transplant patients.

It is therefore essential to be able to accurately assess the presence of abnormalities in bone metabolism by non-invasive techniques and thus to determine whether or not there is a link between them and cardiovascular morbidity and mortality. This allows appropriate management as well as a precise assessment of the impact of new drugs on bone metabolism and the future of transplant patients.

Currently, the clinical management of bone abnormalities includes the use of surrogate biochemical markers such as parathyroid hormone (PTH), bone alkaline phosphatases (bPhA), osteoprotegerin (OPG), the N-terminal propeptide of procollagen type I (P1NP), tartrate resistant acid phosphatase type 5b (TRAP5b), C-terminal collagen type I telopeptides (CTX), osteocalcin and sclerostin. There are conflicting data in the literature as to their correlation with histological and histomorphometric analysis of bone biopsies. These biomarkers tend to take a place in the diagnosis and in the follow-up of patients with abnormalities of bone metabolism, as well as possibly in the detection of vascular calcifications. However, the effectiveness and reliability of this biochemical approach remain to be demonstrated.

On the other hand, imaging techniques allow us to approach the bone structure. They could therefore also be associated with biomarkers to replace bone biopsy. Bone density by bi-photonic x-ray absorptiometry (DEXA) is a relatively accurate and non-invasive screening method for estimating bone mass, mainly trabecular, and which appears to help predict the risk of fracture in kidney transplant patients. DEXA is, however, unable to assess the microarchitecture of bone and only provides a two-dimensional assessment of bone density. The correlation between BMD and fracture risk is, however, much less clear in patients with renal impairment and some studies sometimes even find an absence of correlation. Currently a new software used in DEXA, the Trabecular Bone Score (TBS), seems to help in the assessment of bone microarchitecture. This score is most often weighted with the FRAX to give a better value of the fracture risk. Some data currently appear in the normal population, but no robust data are present in kidney transplant patients.