Pathogenesis and Prevention of Bone Loss in Patients Who Have Kidney Disease and Receive Long-Term Immunosuppression

Abstract

The coexistence of kidney disease with a need for immunosuppressive therapy leads to the convergence of several threats to bone. These comprise general effects of the primary disease, e.g., inflammatory state, more specific effects of acute renal failure or chronic kidney disease, and effects of therapies. Multisystem inflammatory disease that requires immunosuppression is associated frequently with kidney damage, and any reduction of kidney function that takes the patient into or beyond chronic kidney disease stage 2 for more than a short time is likely to have a negative impact on bone health. Bone mineral density frequently is low and fracture rates are high, although correlations often are poor. Chronic inflammation leads to local and systemic imbalance between bone formation and resorption. Upregulation of NF-␤ ligand (RANKL) and variable downregulation of osteoprotegerin are implicated, and bone health may improve in response to treatment of the inflammatory state. Certain immunosuppressive agents, especially glucocorticoids and calcineurin inhibitors, contribute further to bone loss. Antiresorptive agents such as bisphosphonates are used widely and, although able to prevent loss of bone mineral density, have uncertain effects on fracture rates. Augmentation of anabolic activity is desirable but elusive. Synthetic parathyroid hormone is untested but has potential. Manipulation of the RANKL/osteoprotegerin system now is feasible using antibodies to RANKL or synthetic osteoprotegerin. In the future, manipulation of the calcium-sensing receptor using calcimimetic or calcilytic agents may allow the anabolic effects of parathyroid hormone to be harnessed to good effect. With all of these therapies, it will be important to assess response in relation to important clinical end points such as fracture.

Alterations of bone microstructure and strength in end-stage renal failure

“…CtPo was quantified using customized analysis tools [27][28][29] and calculated as the number of void voxels within the cortex. BV/TV is derived from Dtrab assuming that fully mineralized bone has a mineral density of 1,200 mg HA/cm 3 . TbN was defined as the inverse of the mean spacing of the mid-axes.…”

“…Several types of disorders can be observed, ranging from high-turnover (hyperparathyroidism) to low-turnover bone lesions (adynamic bone). In addition to renal failure, CKD-MBD may be worsened from a combination of various factors such as vitamin D deficiency, hyperparathyroidism, malnutrition, the use of certain drugs (corticosteroids, phosphate binders, vitamin D analogs), or hypogonadism [3]. It is associated also with increased morbidity (vascular lesions, fractures, cardiovascular events) and higher mortality [4,5].…”

Bone assessment in children with chronic kidney disease: data from two new bone imaging techniques in a single-center pilot study

“…The deleterious effect of chronic kidney disease (CKD) on bone results from a combination of factors, e.g., vitamin D deficiency, hyperparathyroidism, hypogonadism, malnutrition, resistance to growth hormone and drug toxicity (corticosteroids, calcineurin inhibitors) [1,2]. The impact of CKD on bone and mineral status may be immediate (serum phosphate/calcium disequilibrium) or delayed (fractures, vascular calcifications); bone damage in the spectrum of chronic kidney disease-mineral and bone disorders (CKD-MBD) represents a daily challenge for pediatric nephrologists since it can have long-term consequences.…”

Bone Health and Renal Replacement Therapies: Which are the Best?

“…Kemik mineral yoğunluğu hareketsizlik, D vitamininden fakir beslenme, kronik karaciğer hastalıkları, vaskülitik hastalıklar, kronik böbrek hastalığında ve özellikle uzun süreli immüno-supresif tedavi altında (özellikle kortikosteroid içerikli) artan rezorptif süreç nedeniyle azalmaktadır (55). Bu durum altta yatan primer hastalıkların etkileri, inflamatuvar süreç, akut ve kronik böbrek hastalığındaki birçok sebep ve tedavilerin rezorptif etkileri sonucunda gelişmektedir.…”

“…İmmunosupresif ilaçlardan özellikle glukokortikoidler ve kalsinörin inhibitörleri kemik kaybına neden olmaktadırlar. Antiresorptif ajan olarak kullanılmakta olan bifosfonatlar KMY kaybını önlemekle birlikte fraktür riskini etkilememektedirler (55). Çalışmamızda tüm vücut KMY'nin hemodiyaliz hasta popülasyonunda daha düşük olduğu, diğer gruplar arasında ise benzer olduğu görüldü.…”