Renal osteodystrophy (ROD) is the constellation of skeletal abnormalities found in chronic renal insufficiency,
which can exacerbate with long-term dialysis and renal transplantation.[1],[2]
ROD in transplanted patients has its own pathophysiologic particularities,
since multiple biochemical and hormonal factors regulate mineral metabolism and bone turnover (table 1): the grade of previous ROD is highly variable and the postoperative impact factors include renal function,
disturbances of mineral metabolism,
PTH status,
hypophosphataemia and immunosuppressive drugs.[2],[3]
The spectrum of skeletal abnormalities existent in ROD is related to the state of bone turnover.
High turnover bone disease or osteitis fibrosa cystica is characterized by increased osteoblast and osteoclast activity and is the manifestation of persistent hyperparathyroidism.[2],[4] In fact,
chronic renal failure is the most common cause of secondary hyperparathyroidism,
which is due to compensatory hyperplasia of the parathyroid gland promoted by increased serum phosphate levels and depressed serum calcium levels.[5]
Increased serum parathyroid hormone concentrations are found after renal transplantation,
being greater than twice the normal in more than 50% of patients after 1 year.[3] Persistent hypophosphataemia is also observed respectively in 90% and 20-40% of patients 4 months and 1 year after renal transplantation; it occurs in association with subnormal graft function,
namely decreased phosphate reabsorption in the proximal tubule.[2],[3] These metabolic factors play a crucial role in maintaining a high bone turnover state.[2]
Low turnover bone disease includes osteomalacia and adynamic bone disease. Osteomalacia results from a defective mineralization of newly formed osteoid and is promoted by persistent hypophosphataemia.[3] It affects cortical and trabecular bone,
in areas of stress or along nutrient vessels.[2] Adynamic bone disease reflects a low bone formation rate without a primary mineralization defect and includes osteopenia and osteoporosis.[2],
[6]
Additionally,
prolongated glucocorticoid therapy and other immunosuppressive drugs also promote inhibition of osteoblast activity and activation of osteoclasts in spongy and/or cortical bone,
contributing to the low bone turnover state.[3],[6]
It is postulated that during the first 6 months after transplantation,
there is a rapid decrease in bone mineral density at an estimated rate of 6.8% during the first year,
resulting in a high risk of fracture,
which,
initially,
is even higher than that in dialysis patients.[3] The highest incidence of bone fracture occurs at 2 years post-transplant,
with an absolute risk three times that of age-matched controls.[3] The rate at which bone mass is lost gradually attenuates,
mostly due to the reduction in the dose of steroids,
with a residual annual rate of 1.7% being found by the 10th year after renal transplantation.[3]
Amyloid deposition is more common after prolonged haemodialysis.
In most patients,
renal transplantation and subsequent recovery of renal function can decrease the β2-microglobulin disturbances of bone metabolism,
preventing the progression to amyloid arthropathy.[3],[5] Some authors state that although β2-microglobulin deposits may be detectable 10 years after renal transplantation,
their clinical expression can decrease or even disappear thereafter.
It is estimated that 31% of patients develop carpal tunnel syndrome due to β2-microglobulin deposits.[5]
Avascular osteonecrosis is a common and debilitating complication in renal transplantation patients.
A prospective study noted an incidence of 4% of femoral osteonecrosis detected in MR imaging 6 months after the surgery.[2] Chronic glucocorticoid administration remains the main risk factor for this complication and the femoral head is the most common site involved.[2] It usually occurs 9 to 19 months after surgery and can be multifocal in 50 to 70% of affected patients.[2]
Table 1. Contributing factors to ROD in renal transplantation patients
|
Pre-transplantation factors
(pre-existing bone disease)
|
Post-transplantation factors
|
- osteitis fibrosa
- mixed bone disease
- adynamic bone disease
- osteomalacia
- β2microglobulin amyloidosis
|
- immunosuppressive drugs
- PTH status
- renal function
- disturbances of mineral metabolism (hypercalcaemia,
hypophosphataemia,
hypomagnesaemia)
|