Transplant bone disease

Introduction

Pre-transplant evaluation

Prevention & Treatment

Treatment of AVN and bone pain

References

Kidney

Liver

Heart

Lung

Bone Marrow

Introduction

PRE-TRANSPLANT EVALUATION

Prevention & treatment

Vitamin D stores should be adequate. Recommended amounts are 800 units/day of cholecalciferol. The more active metabolites such as calcitriol may be necessary in patients who have secondary hyperparathyroidism or hypocalciuria. Calcitriol can overcome the steroid-induced decrease in calcium absorption. If used, the urine and serum calcium must be monitored closely, because hypercalcemia or hypercalciuria can occur.

Gonadal hormones Although data from clinical trials in transplant recipients are lacking, it makes physiological sense to treat hypogonadism with testosterone in males and estrogen in females. The route of delivery does not seem to alter bone effects, but the transdermal medicines are preferred in patients with liver transplant to avoid high "first-pass" concentrations in the liver.

In females, regular menstrual periods suggest adequate estrogen; irregular menses are essentially a bioassay for insufficient estrogen. Depot-medroxyprogesterone acetate contraception, which has recently been shown to decrease bone density, should be avoided. Women with a history of breast cancer, hypertriglyceridemia or pulmonary emboli should not be given estrogen.

In males, testosterone should be routinely measured, because it may be low without obvious clinical signs. Hypogonadal males may have smaller prostate size than expected, and with testosterone therapy the prostate may enlarge to the usual size for normal age-matched men. In older men this may cause symptoms and limit the use of testosterone.

Antiresorptive medications Most transplant recipients require corticosteroids to prevent rejection, and physicians already try to keep the dose as low as possible. Several new medications have been studied in other groups of patients with steroid-induced osteoporosis. The experience in transplant recipients is much more limited. Drugs which block bone resorption (bisphosphonates and calcitonin) have been studied most carefully. Some pilot studies of drugs to enhance bone formation (fluoride, growth hormone, PTH) have results that are interesting but not consistent enough to allow recommendation

Bisphosphonates are potent anti-resorbing agents that increase the bone density and reduce fracture risk in postmenopausal women with established osteoporosis. In women with low bone density but without fragility fractures, 4.2 years of alendronate therapy increased bone density but did not change the risk of clinical fractures. Bisphosphonates also increase bone density in steroid-treated patients, but the increase is not as great as in patients with postmenopausal osteoporosis. Studies in steroid-treated patients have not had adequate power to assess fracture prevention.

Physicians should not automatically prescribe bisphosphonates for low bone density, just as they should not give iron to treat every case of anemia. The decision to treat with bisphosphonates should be made individually, weighing the immediate benefit with the known risks and, because these are new drugs, with the potential future risks. The most serious side effect seen with amino-bisphosphonates is esophageal erosion. Patients who are at bedrest should not be given these medications orally. Serious hypocalcemia is also seen in patients treated with bisphosphonates; this is not surprising since these drugs block bone resorption, which may be maintaining the serum calcium level. In patients with secondary hyperparathyroidism caused by malabsorption or renal failure, bisphosphonates worsen the hyperparathyroidism. Theoretically, osteomalacia would become worse with bisphosphonates, but this has been documented only with etidronate, which has an independent adverse effect on mineralization. Bisphosphonates are excreted by the kidney, and thus should be used cautiously in patients with renal insufficiency; elevated creatinine is listed on the label as a contraindication. Effects during pregnancy have only been studied in animals, in which fetal calcium metabolism may be severely altered. Thus, these drugs should be avoided in women who may become pregnant. Acutely, intravenous bisphosphonates decrease the white blood cell count and produce a febrile reaction. Thus, they should not be given to transplant recipients if there is a question about ongoing infection. Fractures appear to heal in animals treated with bisphosphonates, although it takes longer to remodel the callus.

Calcitonin has been used for prolonged time with a good safety profile. The results on bone density in steroid-treated patients or transplant recipients is not as consistent as with bisphosphonates. Calcitonin is an antiresorptive medication and thus could worsen hyperparathyroidism. Calcitonin appears to be a gentler, safer drug that is a good choice for transplant recipients with low risk of fractures.