Bone Disease after Renal Transplantation

Abstract

It has been well established that a rapid decrease in bone mineral density (BMD) occurs in the first 6 to 12 mo after a successful renal transplantation and persists, albeit at a lower rate, for many years. This rapid BMD loss significantly increases the fracture risk of these patients to levels that are even higher than those of patients who have chronic kidney disease stage 5 and are on dialysis. The presence of low BMD in renal transplant patients as a predictor of risk fracture is controversial. Indeed, as has been suggested also for patients with postmenopausal osteoporosis, there is not a compelling correlation between the decline in BMD and skeletal fractures. However, bone disease after renal transplantation probably represents a unique bone disorder that must encompass underlying renal osteodystrophy. In fact, this syndrome results from multiple factors that include pretransplantation bone status, use of glucocorticoids and other immunosuppressive drugs, hypophosphatemia, and alterations of the calcium-vitamin D axis. Recent studies have demonstrated decreased osteoblast number, reduced bone formation rate, delayed mineralization, and increased osteoblast and osteocyte apoptosis. Bisphosphonates and vitamin D metabolites may be valuable in preventing or diminishing early bone loss. However, clinicians should be careful with the use of bisphosphonates and oversuppression of bone, especially in patients with low bone turnover. New prospective, controlled trials are required to confirm the real efficacy of these drugs, particularly in long-term renal transplant patients.Clin J Am Soc Nephrol 1: 1300 -1313, 2006. doi: 10.2215/CJN.01510506 K idney, heart, lung, and liver transplantation have become fairly common and successful. As the number of transplants has grown, new challenges have arisen in the management of long-term complications of transplantation. Posttransplantation bone disease represents one such important complication, because it is observed in a substantial proportion of patients. As a consequence, bone mass loss and bone fractures are common in these patients and cause substantial morbidity.In patients with chronic kidney disease (CKD), renal osteodystrophy that begins during the early stages of the disease usually worsens during dialysis and may persist after transplantation, although in many patients, improvement in these bone lesions are observed. In addition to preexisting bone lesions, not only factors that hamper recovery but also new factors could affect bone structure after transplantation. These include the potential deleterious effects on bone of the different immunosuppressive agents, the impaired renal function that frequently is observed in renal transplant patients, and several others factors that are particular to each patient, such as postmenopausal status, presence of diabetes, gender, and time after transplantation. Changes in Bone Mineral DensityBone mineral density (BMD) as assessed by dual x-ray absorptiometry has been used as a noninvasive method to assess bone mass loss...

Risk factors for fracture in adult kidney transplant recipients

“…We also assessed other fracture locations, defined as: Lower leg (ankle, tibia, fibula, patella), femoral shaft, rib/sternum/ trunk, scapula, clavicle, and pelvis fractures. These fractures as a whole were considered the secondary outcome as they may be more common in kidney transplant recipients [10] . For example, in prior studies ankle fractures were common in kidney transplant recipients [1,19] .…”

“…FRAX is used to guide treatment decisions in the general population by incorporating age, sex, clinical risk factors (body mass index, parental hip fracture, glucocorticoid use, rheumatoid arthritis, smoking, alcohol intake ≥ 3 units per day), and hip bone mineral density (optional) to predict the 10-year probability of hip fracture or major osteoporotic fracture (proximal humerus, forearm, hip, or clinical vertebral) [7][8][9] . However, kidney transplant recipients may have different risk factors for fracture given the unique pathophysiology that underlies their bone disease [10] . For example, in a recent cohort study the only classical risk factor for fracture that reached statistical significance in kidney transplant recipients was high alcohol use [11] ; however, this study had only 21 fracture events and may have had inadequate statistical power to identify other risk factors [11] .…”

Bone Disease after Kidney Transplantation

“…Earlier studies after transplantation indicate that bone mineral density (BMD) declines by 4%-10% in the first 6 months (2), with a further decrease of 0.4%-4.5% in lumbar BMD between 6 and 12 months (3). More recent publications of prospective trials that included patients managed with contemporary immunosuppression protocols have reported bone loss of only 0.1%-5.7% in the lumbar spine (4). After 1 year, BMD remains relatively stable with no further decline but at significantly lower levels than healthy controls (2).…”

Paricalcitol for Secondary Hyperparathyroidism in Renal Transplantation

“…[3][4][5] Several factors involved in the pathogenesis of post-transplant CKD-MBD include immunosuppressive therapy, especially corticosteroids, 6 hormonal disturbances, and progressive deterioration of graft function. 7 Secondary hyperparathyroidism (SHPT) has been consistently reported to play a central role in posttransplant CKD-MBD. [8][9][10][11] Most of the clinical and laboratory abnormalities of SHPTseem to be largely explained by enhanced intact parathyroid hormone (iPTH) production.…”