Managing Bone Disease in Kidney Transplant Recipients

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Organ transplantation has become a fairly common and effective modality for the treatment of several types of end-stage conditions, including chronic kidney disease (CKD).


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Advances in immunosuppressive agents and transplant techniques have led to improved long-term graft and patient survival. Successful transplantation is capable of reversing many complications of end-stage kidney disease; however, disturbances of bone and mineral metabolism may persist, while new bone disorders may also emerge as a result of transplant-related medications such as corticosteroids.

Particularly during the early post-transplant period, renal allograft recipients experience a rapid loss of bone mass. Although bone disease has been recognized as a common complication in kidney transplant recipients, the routine application of adequate diagnostic tools as well as treatment to prevent further bone loss is often insufficient.

In this review article, we have summarized the updated information about prevalence, consequences, and therapeutic options of mineral and bone disorders (MBD) in kidney transplant recipients.


Prevalence of Renal Osteodystrophy by Type


Renal osteodystrophy is traditionally classified into four major groups: hyperparathyroid bone disease, adynamic bone disease, mixed renal osteodystrophy, and osteomalacia.1,2 Table 1 shows the main characteristics of different types of MBD in kidney transplant recipients.

The precise histologic patterns of bone disease after transplantation are not well defined because only in very few studies was the bone biopsy performed in kidney transplant recipients. The results of the few early reports on the bone abnormalities in patients after renal transplantation are somewhat conflicting.

Heterogeneity of bone lesions has been noted in these early studies,3,4 whereas others report a high prevalence of: high bone turnover associated with persistence of secondary hyperparathyroidism;5 normal bone formation;4 or low bone turnover.6,7 Prolonged mineralization lag time without osteoid accumulation has been found in some studies,6-8 whereas frank osteomalacia has rarely been observed.3

The bone biopsy studies from the modern immunosuppressive era (21st century) suggest that the adynamic bone disorders and mixed renal osteodystrophy are the two most common abnormalities in kidney transplant recipients. In a study of 57 unselected prevalent kidney transplant patients, cancellous bone volume/tissue volume was below normal compared with 56% of age- and gender- matched control subjects.9

Bone turnover was low in 46%, normal in 28%, and elevated in 26% of patients. Mineralization was prolonged in 88% of patients, including nine with osteomalacia and 12 with focal osteomalacia.9 Similar results were found in 20 patients examined before and after kidney transplantation.10 Bone histomorphometric diagnoses at pre-transplant were adynamic bone disease (12 patients); mixed bone disease (three patients); mild disease (three patients); and osteitis fibrosa (two patients). After transplantation, 11 patients had adynamic bone disease, eight with mild disease. One patient had osteomalacia.10

However, the opposite results were found in a study from Germany.11 Mild osteitis fibrosa and osteitis fibrosa, the most frequent forms of renal osteodystrophy, were observed in 13 (22.8%) and 14 patients (24.6%), respectively. Mixed uremic osteodystrophy was found in seven patients (12.3%), adynamic renal bone disease in three patients (5.3%), and osteomalacia in two (3.5%).11 In 13 patients (22.8%), reduced bone mass and structural damage without typical signs of renal osteodystrophy, such as endosteal fibrosis or osteoclasia, were detected, and five patients (8.7%) showed normal histomorphometric parameters.11

Hence, in stable kidney transplant recipients low turnover bone disease (adynamic and osteomalacia) is the most common bone disorder. These patients exhibit decreased mineral apposition rate and delayed mineralization explained by the dramatic decrease in parathyroid hormone (PTH) levels in patients with relatively mild bone disease before transplantation6 and high dose of glucocorticoids.9

Moreover, a study by Velasquez-Forero et al. showed mainly alterations that were consistent with adynamic bone disease and increased deposition of iron in the mineralization front;7 other studies have shown decreased bone formation and prolonged mineralization lag time in the presence of persisting bone resorption.8

There are discrepancies among the findings described in various studies, but the main alterations in bone remodeling after renal transplantation appear to consist of a decrease in bone formation and mineralization in the face of persistent bone resorption, producing an imbalance in remodeling and favoring resorption. Likewise, the defective bone formation may be a consequence of alterations in osteoblast function, decreased osteoblastogenesis, or increased osteoblast death rate.