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Bone mineral density Z-scores in four different compartments in heart, kidney, liver and lung transplant groups. *p < 0.05, **p < 0.001. Prox, proximal one third of the radius; UD, ultradistal radius.
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Serum osteocalcin and C-terminal telopeptides of type-1 collagen (CTX-1) are known markers of bone turnover, whereas the role of fibroblast growth factor 23 (FGF-23) is yet unknown. We investigated early changes in bone mass and the association of these biochemical markers and FGF-23 with bone loss following renal transplantation (RTx).
In 44 first...
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Citations
... If so, we may be able to take actions such as strict medical or surgical control of HPT before or after transplantation to avoid the detrimental effects of hypophosphatemia and hypercalcemia. The role of FGF23 as an indicator of post-transplant CKD-MBD has not been evaluated extensively [19]. From this study, it could be postulated that interventions to lower FGF23, iPTH and cCa at the time of dialysis would prevent hypophosphatemia and/or hypercalcemia after KTx. ...
Kidney transplantation (KTx) restores many of the disorders accompanying end-stage renal failure. However, hypercalcemia and hypophosphatemia are both common complications after renal transplantation. Prospective observation of these complications has not been well described and pre-transplant predictors also remain unknown. This prospective observational cohort study was carried out to clarify pre-transplant risk factors of persistent hypophosphatemia and/or hypercalcemia at 12 months after transplantation.
Consecutive living donor KTx recipients (n = 39) at Tokyo Women's Medical University were prospectively recruited. Parameters of bone and mineral metabolism including intact parathyroid hormone (iPTH) and full-length fibroblast growth factor (FGF) 23 were followed.
FGF23 decreased to comparable levels for renal function while hyperparathyroidism persisted at 12 months after transplantation. Multivariate linear regression analysis revealed that pre-transplant iPTH correlated with hypercalcemia at 12 months and pre-transplant FGF23 was the best pre-transplant predictor of persistent hypophosphatemia at 12 months.
It is intriguing that although FGF23 is not a causal factor for hypophosphatemia at 12 months post-transplantation, it is a significant predictor of this common complication.
... This is not surprising because changes in bone mass are always more obvious in trabecular compared with cortical bone (22). This observation conflicts with a recent study showing no association between serum FGF-23 levels and BMD loss in incident renal transplant recipients (23). It should be of note that the small patient number (n ϭ 44) and short follow-up (10 weeks) in that study confers an increased risk for a type II statistical error. ...
Among the multiple factors contributing to bone mineral density (BMD) loss after renal transplantation, hypophosphatemia is increasingly recognized to play an important role. Hypophosphatemia occurs in up to 90% of the renal transplant recipients in the early post-transplant period and is caused by renal phosphate wasting. We hypothesized that a high pretransplant level of the recently described phosphaturic hormone fibroblast growth factor 23 (FGF-23) is a risk factor for accelerated BMD loss occurring within the first post-transplant year.
We performed a two-center observational retrospective cohort study in 127 incident renal transplant recipients. Serum full-length FGF-23, parathyroid hormone (PTH), and parameters of mineral metabolism were determined at the time of transplantation. BMD was assessed by osteodensitometry at the time of transplantation and 1 year later.
A moderate decrease of BMD was observed during the first post-transplant year. High FGF-23 levels were associated with BMD loss at the lumbar spine and total hip region, whereas low PTH levels were associated with BMD loss at all three regions. Cumulative doses of prednisone and post-transplant serum phosphate level were not correlated with BMD changes.
Our data indicate that patients with a high serum FGF-23 level and/or a low PTH level at the time of transplantation are at risk for increased BMD loss during the first post-transplant year.
Despite improvement in some chronic kidney disease (CKD) metabolic derangements of bone and mineral metabolism after kidney transplantation, bone disease remains a significant problem. Kidney transplant recipients are at increased risk of bone mineral density (BMD) loss, fractures, and osteonecrosis, all of which are associated with substantial morbidity [1–11]. The pathogenesis of post-transplant bone disease is multifactorial [12–32], including but not limited to interactions of the complex abnormalities in pre-transplant mineral homeostasis [12] and renal osteodystrophy [24, 25], the degree of persistently impaired kidney function, peri-transplant alternations in calciotropic and phosphotropic regulatory hormonal pathways [26], and the potential deleterious skeletal effects of immunosuppressive therapy [27–32].
Management of post-transplant bone disease is challenging given the limitations of the available diagnostic methods and the lack of proven benefit of available therapies to reduce fractures [33]. Despite the evidence that both bisphosphonates and vitamin D receptor agonists (VDRA) attenuate the loss in BMD following successful kidney transplantation, these agents have not been clearly shown to reduce fractures [33–49]. Moreover, there is no consensus on how to monitor the response to therapy and the optimal duration of therapy is unknown. Therefore, therapeutic decisions should be guided by consideration of the interplay of multiple factors including the severity of BMD loss, the presence of risk factors for osteoporotic fragility fractures, disordered mineral metabolism, underlying bone disorder, and the level of kidney function. This chapter provides an approach to screening and diagnosis of post-transplant bone disease and an overview of treatment options.
Patients with chronic kidney disease (CKD) develop secondary hyperparathyroidism, which is a consequence of phosphorus retention, decline in serum calcium levels, and decreased calcitriol production. Increased parathyroid hormone (PTH) synthesis and secretion result in renal osteodystrophy. PTH and vitamin D were previously considered the major factors regulating calcium and phosphate homeostasis. The discovery of FGF-23 has provided a new insight into the disorder of calcium and phosphate metabolism in CKD. FGF-23 is secreted by osteoblasts in response to a phosphorus load, high calcitriol levels and an increased PTH levels. FGF-23 causes both an increase in urinary phosphorus excretion and a reduction in calcitriol synthesis. The reduction in calcitriol levels caused by FGF-23 leads to an increase in PTH production and secretion. High PTH level would result in increased FGF-23 levels. The identification of FGF-23 opens a new field for clinical and experimental research in phosphate homeostasis. There are several feedback loops, involving parathyroid glands, bone, and kidney, regulating serum phosphate concentration. We will review the physiologic function of FGF-23 and its role in calcium and phosphate homeostasis and secondary hyperparathyroidism.
Kidney transplantation, the most effective treatment for the metabolic abnormalities of chronic kidney disease (CKD), only partially corrects CKD-mineral and bone disorders. Posttransplantation bone disease, one of the major complications of kidney transplantation, is characterized by accelerated loss of bone mineral density and increased risk of fractures and osteonecrosis. The pathogenesis of posttransplantation bone disease is multifactorial and includes the persistent manifestations of pretransplantation CKD-mineral and bone disorder, peritransplantation changes in the fibroblast growth factor 23-parathyroid hormone-vitamin D axis, metabolic perturbations such as persistent hypophosphatemia and hypercalcemia, and the effects of immunosuppressive therapies. Posttransplantation fractures occur more commonly at peripheral than central sites. Although there is significant loss of bone density after transplantation, the evidence linking posttransplantation bone loss and subsequent fracture risk is circumstantial. Presently, there are no prospective clinical trials that define the optimal therapy for posttransplantation bone disease. Combined pharmacologic therapy that targets multiple components of the disordered pathways has been used. Although bisphosphonate or calcitriol therapy can preserve bone mineral density after transplantation, there is no evidence that these agents decrease fracture risk. Moreover, bisphosphonates pose potential risks for adynamic bone disease.
