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CLINICAL REVIEW |
Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center (N.M.M.), Dallas, Texas 75390; and Department of Medicine, Columbia-Presbyterian Medical Center and College of Physicians and Surgeons, Columbia University (E.S.), New York, New York 10032
Address all correspondence and requests for reprints to: Dr. Elizabeth Shane, Department of Medicine, College of Physicians and Surgeons, Columbia University, PH8–864, 630 West 168th Street, New York, New York 10032. E-mail: es54{at}columbia.edu.
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Abstract |
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 Top Abstract IntroductionPathogenesis of Transplantation...ConclusionsReferences |
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Introduction |
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TopAbstractIntroductionPathogenesis of Transplantation...ConclusionsReferences |
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) (1). Thus, the total number of patients who have undergone solid organ transplantation now exceeds 300,000 in the United States alone. With the increasing number of organs transplanted and the improved survival of transplant recipients, bone disease has emerged as a common complication of the transplantation process. Osteoporosis is found in up to half of transplant recipients, and vertebral fractures are present in almost a third of the patients in some centers (2).
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Pathogenesis of Transplantation-Related Osteoporosis |
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TopAbstractIntroductionPathogenesis of Transplantation...ConclusionsReferences |
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). In this section, these factors are examined and discussed separately, although one should keep in mind that they are all intertwined in the context of organ transplantation.
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Candidates for organ transplantation often suffer from fractures and/or osteoporosis. Advanced age, poor nutrition, immobility, hypogonadism, cachexia, and lifestyle factors (smoking and alcohol abuse) frequently contribute to the poor skeletal health of patients with organ failure requiring transplantation. In addition, hepatic, pulmonary, cardiac, and renal failure have unique pathophysiologies that affect bone health before transplantation. These particular features are examined in this section.
Hepatic osteodystrophy
Osteoporosis and fractures are relatively common findings in patients with chronic liver disease (3). Osteoporosis is found in 37–53% of cirrhotic patients referred for liver transplantation (4, 5, 6). Osteoporosis is seen more often in primary biliary cirrhosis, in part because this condition mostly affects postmenopausal women, a patient population already at risk for osteoporosis (7). A wide range of vertebral fracture rates (3–44%) has been reported among cirrhotic patients; the disparities among the studies are probably due to differences in the populations examined (8). In some reports, bone histomorphometry studies have shown decreased bone volume accompanied by a reduction in parameters that reflect bone formation (osteoblast number, osteoblast surface area, and bone formation rate) (9, 10) and, in some reports, increases in parameters reflecting bone resorption (osteoclast number and bone resorption surface) (10, 11).
Reduced bone formation in chronic liver disease has been ascribed to several factors, including excessive alcohol use (12), decreased IGF-I levels (13), and hyperbilirubinemia (14). The increased bone resorption seen in some patients with advanced liver disease has been partly attributed to hypogonadism (6, 15), a frequent finding in cirrhotic patients. Additional contributory factors include vitamin D deficiency and glucocorticoid use (3). Osteomalacia is a rare cause of reduced bone mineral density (BMD) in hepatic osteodystrophy (3, 16).
Osteoporosis in end-stage pulmonary disease
Patients with end-stage pulmonary disease commonly have osteoporosis (17, 18), and radiological evidence of vertebral fractures is seen in up to 29% of patients (17, 19). Risk factors for osteoporosis in these patients include smoking, decreased ambulation, low body weight, and glucocorticoid use (20). Cystic fibrosis is associated with additional risk factors, such as hypogonadism (21), malnutrition, inflammatory bone-resorbing cytokines (22), and pancreatic insufficiency that may impair the absorption of calcium and vitamin D (23, 24). Rarely, osteomalacia is a cause of low BMD in adults with cystic fibrosis (25, 26). These patients typically have elevated bone resorption markers, with normal bone formation markers compared with healthy controls (27). In cystic fibrosis, the predominant finding on bone histomorphometry is reduced cancellous bone area and osteoblast number (25, 26), whereas abnormalities in osteoclast number and activity are not universal findings (25, 26).
Bone disease in congestive heart failure
Low BMD is frequently found in patients with congestive heart failure (CHF) (28, 29). In one study, 14% of CHF patients awaiting transplantation had radiological evidence of vertebral compression fractures (29). Of 101 patients with severe CHF (New York Heart Association functional classes III and IV) referred for evaluation for cardiac transplantation, osteoporosis at the femoral neck (FN) was seen in 19%, and osteopenia was found in another 42% (28). Factors associated with CHF and its therapy that may contribute to bone loss include low serum 25-hydroxyvitamin D (25-OHD) (28), hypogonadism, long-term heparin and/or loop diuretic administration, mild renal insufficiency and secondary hyperparathyroidism (30).
Renal osteodystrophy
Bone disease is found in virtually all patients with chronic kidney disease once the glomerular filtration rate falls below 60 cc/min (31, 32). Compared with the general population, end-stage renal disease (ESRD) patients are 4.4-fold more likely to sustain a hip fracture, and the prevalence of vertebral fractures is as high as 21% (33). Risk factors for fractures in ESRD include older age, female gender, and duration of dialysis (34, 35). The pathogenesis of renal osteodystrophy is complex, and several mechanisms contribute to the poor skeletal health. The gold standard in the diagnosis and classification of skeletal lesions in renal osteodystrophy remains quantitative histomorphometry of transiliac crest bone biopsies after tetracycline labeling, an invasive procedure that, unfortunately, is of limited availability (31). Based on histological features, renal osteodystrophy is classified as osteitis fibrosa, osteomalacia, adynamic disease, or mixed types (Table 1) (32). Osteitis fibrosa, mainly caused by secondary hyperparathyroidism, is characterized by increased bone turnover and osteoclast activity resulting in increased resorption depth. The characteristic finding in osteomalacia is a mineralization defect with accumulation of unmineralized osteoid and low rates of bone turnover. Adynamic renal bone disease is characterized by decreased remodeling activity, and its pathogenesis remains poorly understood. Hypogonadism, ß-microglobulin amyloidosis, and medications (such as glucocorticoids, heparin, and cytotoxic drugs) are all additional factors that may adversely affect skeletal health in ESRD. It should be stressed that measurement of BMD cannot be applied to the diagnosis of osteoporosis in patients with ESRD, because this technique does not distinguish among the various histological lesions that may be present.
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Glucocorticoids. Glucocorticoids play a major role in the bone loss following transplantation. High doses are usually prescribed immediately after transplantation, and the dose is then gradually tapered over the next few months. Additional doses are often given for the management of episodes of rejection.
The etiology of glucocorticoid-induced osteoporosis is multifactorial (Fig. 3). Early on, a phase of rapid bone loss is seen (36), probably secondary to increased bone resorption due to a combination of renal calcium wasting (37), decreased intestinal absorption of calcium (38), and hypogonadotropic hypogonadism (39, 40). In addition, glucocorticoids directly promote osteoclastogenesis by increasing receptor activator of nuclear factor-
B ligand and decreasing osteoprotegerin (41). With both acute and chronic use, bone formation is profoundly inhibited, because glucocorticoids reduce osteoblast proliferation, function (by inhibiting the expression of the genes for osteocalcin, type 1 collagen, and IGF-I) (41), and life span (by promoting osteoblast apoptosis) (42). In addition to their direct effects on the skeleton, glucocorticoids can induce a profound myopathy (43), impairing balance and mobility, decreasing weight-bearing activity, and increasing fall risk and the potential for fractures.
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In murine models, calcineurin inhibitors cause high turnover osteoporosis (45). CSA stimulates both osteoclast and osteoblast activity in vivo, but resorption rates exceed formation rates, with a net loss in bone mass (46, 47). A major side-effect of CSA therapy is dose-related, acute and chronic nephrotoxicity, often leading to secondary hyperparathyroidism (48), which may also adversely affect skeletal health. Interestingly, CSA-induced osteopenia is attenuated by parathyroidectomy (49). Tacrolimus, a fungal macrolide, also induces severe trabecular bone loss in rats (45), although this bone loss may be less severe in humans compared with that induced by CSA (50).
Other immunosuppressive agents.
Other immunosuppressive agents may also affect bone metabolism, although the information available is limited. Mycophenolate mofetil (51), rapamycin (52), and azathioprine (53) have shown no effects on bone volume in the rat model (Table 2).
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During the ever-longer times on the transplant waiting list, many patients experience progressive disease-related decompensation associated with reduced physical activity and malnutrition. In the absence of appropriate interventions, these complications can adversely impact skeletal health (54). Interestingly, the severity of bone loss correlated with prolonged in-hospital stay after transplantation (55).
Hypothalamic-pituitary-gonadal (HPG) axis after transplantation
In many heart transplant recipients, testosterone levels fall immediately after transplantation, but generally normalize within the first year (56). Despite significant alterations in the HPG axis and sex steroid metabolism before liver transplantation, physiological function resumes in the majority of patients after transplantation (15, 57). Normal menses resume in 48–80% of women, particularly those who were transplanted for acute liver failure (58, 59). Renal transplantation corrects the hyperprolactinemia induced by uremia and is followed by restoration of the HPG axis in many men and premenopausal women (60, 61). There is no published information on gonadal function in lung transplant recipients.
Vitamin D and PTH after transplantation
Prospective studies in lung, heart, and liver transplant recipients indicate that serum 25-OHD levels tend to gradually increase from the low levels seen before transplantation to normal levels, although this is probably related to the use of vitamin D supplements (18, 56, 62). A progressive increase in the serum PTH concentration was noted in liver transplant recipients followed prospectively (15, 62), whereas no change was noted in the mildly elevated PTH levels after cardiac transplantation (56). The mechanisms underlying the elevated serum PTH levels are not well established, but may be related in part to the decline in renal function seen in up to 20% of transplant recipients (63).
In renal transplant recipients, serum PTH concentrations decrease progressively during the first 6 months after transplantation (64). However, persistent hyperparathyroidism is detected in 25–43% of patients with a serum creatinine level below 1.5 mg/dl 1 yr after grafting, probably due to the slow involution of the hyperplastic parathyroid glands (65, 66). Pretransplant risk factors for persistent hyperparathyroidism in renal transplant recipients are longer time on dialysis and higher PTH levels (67). Posttransplantation predictors include glomerular filtration rate less than 70 ml/min, use of CSA, and low serum 25-OHD levels (68, 69).
Bone loss and fractures after transplantation
BMD after transplantation.
After solid organ transplantation, large decreases in BMD at the lumbar spine (LS) and FN are observed during the first year. This decrease occurs mainly in the first 3–6 months (15, 56, 70, 71), and is probably related to the large doses of glucocorticoids used immediately after grafting (Fig. 4) (3, 72). Early bone loss involves the LS (cancellous bone), a finding typical of glucocorticoid-induced bone loss. Rates of LS bone loss slow thereafter, with stabilization by 6–12 months and even some recovery after liver, lung, and heart transplantation. One study reported continued increases in BMD up to 7 yr after liver transplantation (62). After the first 6 months, FN bone loss may exceed that at the LS, and most studies do not document any recovery of bone mass at the hip. Reports on BMD changes after renal transplantation differ somewhat. The rapid and significant early loss in BMD in the first 6 months (71) may be followed by continued loss of approximately 1% yearly, up to 8 yr after renal transplantation (73).
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) (74, 75, 76). After renal transplantation, the incidence of fracture remains elevated, consistent with the persistent decline in BMD (Fig. 5) (77). Fractures of the spine and ribs are more likely after lung, cardiac, and liver transplantation (70, 75), whereas kidney transplant recipients experience relatively more fractures of the long bones and feet (78). Risk factors for fractures after transplantation include older age, prevalent fractures before transplantation, postmenopausal status, and lower body mass index (74, 75, 76, 77). Additional risk factors in renal transplant recipients include the presence of diabetes mellitus and prolonged dialysis (79). The predictive roles of pretransplantation BMD (80) and cumulative glucocorticoid dose (73, 77, 81) are controversial. Serial measurements of BMD at the LS were not found to predict fracture risk after liver (82) or heart (75) transplantation.
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Bone histomorphometry after transplantation
The only bone histomorphometric data on lung transplantation patients come from postmortem vertebral bone biopsy specimens from 11 posttransplant cystic fibrosis patients (mean time from transplantation to death, 29 months) (26). There was severe osteopenia in both trabecular and cortical bone, with decreased osteoblast and increased osteoclast activities (26). Data on bone biopsies in cardiac transplantation are also scarce. The only study included six patients evaluated at varying times after transplantation, and the histomorphometric findings varied considerably (84). More information is available on liver transplant recipients (85, 86, 87, 88), in whom there was an increase in bone resorption at 3 months after transplantation, accompanied by a more robust increase in parameters of bone formation (osteoblast number and osteoid surface and volume) (85). However, these data may only apply to liver transplant patients in whom osteoblast function is profoundly depressed before transplantation. Several publications have reported the evolution of histological bone findings in renal transplant recipients (66). The findings vary widely, although the predominant lesion was characterized by low formation associated with a normal/high bone resorption (89, 90).
Prevention and treatment of transplantation-related osteoporosis: pretransplantation measures
Identification and correction of risk factors. All transplant candidates should be evaluated and treated before transplantation, because bone disease is common in these patients. Because waiting periods on transplant lists can be as long as 1–2 yr, there is time to implement measures to improve skeletal health. Lifestyle factors, such as immobilization, smoking, and alcohol abuse, should be addressed. The use of medications that can negatively impact skeletal health should be assessed and minimized to the extent possible. Other factors that can be corrected include hypogonadism and negative calcium balance. Evaluation and treatment of renal osteodystrophy according to accepted guidelines (31) are recommended for all patients with ESRD.
All patients should receive the recommended daily allowance for calcium (1000–1500 mg/d) and vitamin D (400–800 IU/d). It is unclear whether treatment of osteoporosis present before transplantation decreases the incidence of fractures posttransplantation, because controlled studies regarding this issue have not been conducted. However, antiresorptive agents may help improve BMD in liver and heart transplant candidates and reduce fractures in other populations, and their use can be supported on these bases. There is widespread concern that bisphosphonates may increase the risk of adynamic bone disease in ESRD patients, and they are not approved for the treatment of these patients (91).
Measurement of BMD. Lower BMD before transplantation has been cited as a risk factor for fractures after transplantation in some studies (76), although this has not been confirmed by other reports (75, 80). Nevertheless, BMD measurement is recommended by the American Gastroenterological Association (8), the Kidney Disease Outcomes Quality Initiative Group (92), and other researchers (2, 3, 93, 94). In our view, it should be used to detect osteoporosis that exists before transplantation and can be helpful in selecting patients who would benefit from immediate initiation of therapy. In patients with normal BMD, such therapy could be safely deferred until the time of transplantation. The interpretation of BMD measurements is difficult in the setting of renal bone disease, and the World Health Organization criteria for diagnosis of osteoporosis should not be used in these patients. Similarly, osteomalacia, a rare occurrence in patients with cystic fibrosis or severe hepatic failure, may lead to a low BMD in the absence of osteoporosis.
Prevention of early posttransplantation bone loss
Because rates of bone loss and fracture incidence are highest immediately after transplantation, preventive and therapeutic measures should be instituted at that time and without delay. In addition, the lack of reliable clinical predictors to identify individual patients who will experience osteoporotic fractures renders all transplant recipients candidates for preventive therapy. Prevention trials in posttransplantation osteoporosis are limited by their inclusion of small numbers of subjects, the absence of fracture data, the lack of randomization, and their performance in single centers in most studies, which may limit the generalization of results.
Exercise. The importance of physical activity in restoring BMD is demonstrated in three prospective, randomized, albeit very small, studies conducted in heart (95, 96) and lung (97) transplant recipients. These reports show that specific resistance training restored BMD toward pretransplantation levels more rapidly (95, 97) and, in conjunction with alendronate, was more efficacious than alendronate alone (96).
Calcium and vitamin D. Replacement doses of calcium and vitamin D (up to 1000 IU daily) do not prevent clinically significant bone loss after transplantation, as demonstrated by the control arms of several trials studying the effects of different medications (19, 56, 98). Moreover, trials that have demonstrated efficacy of other medications have generally been conducted in the setting of calcium and vitamin D repletion, and it is our opinion that all transplant recipients should receive 1000 mg elemental calcium and at least 400 IU vitamin D daily.
Vitamin D metabolites. Calcium and calcidiol (25-OHD) therapy was associated with an increase in BMD levels or prevention of additional bone loss in heart (99) and renal (100) transplant recipients. The effects of calcitriol with calcium have been controversial. At doses averaging 0.25 µg daily, calcitriol did not significantly prevent LS bone loss in kidney (101) and heart (102) transplant recipients. Studies of calcitriol therapy at doses of 0.5 µg daily or higher have found variable results. In a 2-yr, randomized, double-blind study, calcitriol (0.5–0.75 µg/d) reduced proximal femur bone loss in heart and lung transplant recipients (103). Despite no diminution of LS bone loss, calcitriol reduced the occurrence of vertebral fractures/deformities, although not significantly (103). In another study, calcitriol (0.5 µg/d) reduced bone loss at the total hip, FN, and LS in 75 heart transplant recipients compared with an untreated reference group (83). At doses of 0.5 µg or higher, calcitriol commonly causes hypercalcemia and hypercalciuria (seen in >50% of patients), which may develop at any time during therapy. Close monitoring of serum and urinary calcium is required (83, 103).
Calcitonin. Calcitonin is ineffective in preventing early bone loss after transplantation (10, 102, 104, 105).
Bisphosphonates.
Bisphosphonates are indicated for the prevention of glucocorticoid-induced osteoporosis, and their antiresorptive mechanism of action makes these drugs the obvious choice to prevent the increased bone resorption and rapid bone loss early after transplantation (Fig. 4). Several clinical trials have confirmed this benefit.
Compared with placebo, pamidronate (0.5 mg/kg), given as two iv infusions at the time of renal transplantation and 1 month later, prevented bone loss at the FN and LS at 1 yr (106); the protective effect at the hip was apparent even 4 yr after transplantation (107). Similar results have been reported with repeated iv doses of pamidronate in a controlled randomized study of 34 pulmonary transplant recipients (108) and in nonrandomized studies of heart (109), lung (98), and liver transplant recipients (110). However, in a recent study of liver transplant recipients, a single dose of 60 mg pamidronate, iv, had no significant effect on fracture rate or BMD change posttransplantation compared with placebo (111). The administration of pamidronate as early as 3 months before transplantation in some patients may explain this finding. Alternatively, pamidronate might have prevented the increase in bone turnover that occurs in untreated patients after liver transplantation, as demonstrated by paired histomorphometry studies (86). In a study of renal transplant recipients, repeated doses of iv pamidronate preserved vertebral BMD during treatment and 6 months after cessation of treatment (112). However, pamidronate treatment was associated with development of adynamic bone histology (Fig. 6) (112).
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Cyclical etidronate has been studied extensively, but has fallen out of favor since the introduction of newer, more potent bisphosphonates. Two 4-mg iv doses of zoledronic acid given to 20 patients at 2 wk and 3 months after renal transplantation led to higher BMD values than placebo at 6 months, but not at 3 yr (114). Another bisphosphonate not yet approved for the treatment of osteoporosis in the U.S. has also been studied. Ibandronate given iv with calcium had protective effects on BMD in liver (115) and kidney (116) transplant recipients compared with calcium supplementation alone. However, no fracture data are available.
In summary, oral and iv bisphosphonates, in conjunction with calcium and vitamin D, are effective in preventing posttransplantation bone loss when started shortly after grafting. The optimal dose, timing, and frequency, particularly of iv bisphosphonate administration, remain to be determined. No reports to date demonstrate unequivocal protection from fractures. Their use after pediatric transplantation and in patients with poor renal function should be considered carefully. Finally, the risk of inducing or prolonging adynamic bone disease in renal transplant recipients, especially with repeated dosing, must be kept in perspective. However, we recommend their use after renal transplantation, at least for the 6 months when rates of bone loss are most rapid.
Treatment of bone loss in long-term transplant recipients
Despite the evidence for the benefit of antiresorptive therapies instituted shortly after transplantation, many transplant recipients do not receive such therapies and have established osteoporosis and/or persistent ongoing bone loss. Several studies have examined treatment options for these patients.
Vitamin D metabolites. One study has shown that calcitriol (0.5 µg/d) is superior to calcium therapy alone in preserving LS bone mass in renal transplant recipients who were started on treatment approximately 3 yr after grafting (117). In contrast, calcitriol (0.25 µg/d) and calcium did not significantly improve BMD in long-term renal transplant recipients compared with the effect of no treatment (118). Similarly, calcitriol treatment did not result in additional improvement in LS BMD compared with calcium supplementation alone in two studies of cardiac transplantation recipients enrolled at 6 months (119) or 35 months (120) after grafting, although the interpretation of these two studies is confounded by the use of concomitant hormone therapy replacement in hypogonadal patients.
Calcitonin. Although ineffective in preventing early bone loss, calcitonin may have some benefit in the later posttransplant period in liver (121) and renal (122) transplant recipients and can be considered a safe alternative if other agents are contraindicated or poorly tolerated.
Bisphosphonates. Pamidronate (30 mg, iv, every 3 months for 2 yr) was studied in 13 cardiac and 21 liver transplant recipients with osteoporosis, in whom it was initiated approximately 2 yr after transplantation. Significant gains in LS and FN BMD were noted compared with historical controls (123). One year of oral clodronate (1600 mg/d) initiated 6 months after transplantation in 64 cardiac transplant recipients with low BMD induced a significant increase in LS BMD at 1 yr (124). In renal transplant recipients with low bone mass, cyclical therapy with a lower dose of clodronate (800 mg/d) did not result in significant changes in spine BMD compared with calcium alone (122). Alendronate (10 mg/d) started approximately 5 yr after renal transplantation was associated with significant gains in BMD (125). In long-term renal transplant recipients, alendronate resulted in significant increases in FN and LS BMD, although the increase in BMD did not differ between alendronate and calcitriol treatments (126, 127).
In an uncontrolled study of 58 long-term kidney transplant recipients more than 1 yr postgrafting, alendronate decreased the rate of bone loss and increased BMD over 1 yr in patients with high bone turnover and either osteoporosis or osteopenia (128). In the same study, patients considered at low risk for fractures (based on normal BMD and bone turnover markers) were followed untreated and did not lose any additional bone mass over 1 yr (128). Although uncontrolled, this study may be helpful in guiding the therapy of long-term transplant recipients and identifying those who may benefit from bisphosphonate therapy beyond the first year posttransplantation. Although bisphosphonates appear to increase BMD in long-term heart, liver, and kidney recipients, fracture reduction has not been demonstrated.
Gonadal hormone replacement. Replacement of sex steroids is known to increase BMD in hypogonadal women and men with osteoporosis, although limited published information is available for transplant recipients. Transdermal estradiol was shown to improve LS and FN BMD in an uncontrolled study of postmenopausal liver transplant recipients followed for 2 yr (129). In another uncontrolled report, testosterone replacement, started 6 months after cardiac transplantation in hypogonadal men who were also receiving calcium and vitamin D, stabilized BMD at the LS within 24 months (120). Risks associated with gonadal replacement (130, 131) should be kept in perspective when considering this modality in transplant recipients.
Other strategies for prevention and treatment of bone loss in transplant recipients
PTH. Recombinant human PTH-(1–34) is the only anabolic agent currently approved in the U.S. for the treatment of postmenopausal osteoporosis. It has been shown to improve BMD in patients with glucocorticoid-induced osteoporosis after 1 yr of treatment (132). In the future, PTH may play a role in the management of transplantation osteoporosis, although its usefulness may be limited because of the secondary hyperparathyroidism commonly observed in long-term transplant recipients.
Glucocorticoid-free and calcineurin inhibitor-free regimens. Glucocorticoids have been associated with several side-effects in transplant recipients, including transplantation-related osteoporosis. This has led different investigators to evaluate immunosuppressive regimens that minimize exposure to glucocorticoids by tapering them more rapidly and eventually withdrawing them (133). Glucocorticoid withdrawal accelerated the recovery of bone mass in liver (134) and renal (135) transplant recipients. However, a metanalysis evaluating the effects of prednisone withdrawal suggested that the occurrence of acute rejection and graft loss was greater than that in control patients, dampening the enthusiasm for this practice (136). The introduction of newer immunosuppressants may lead to glucocorticoid avoidance or more rapid dose reduction, although long-term data are lacking.
Minimizing the use of calcineurin inhibitors could potentially reduce the incidence of acute and chronic nephrotoxicity (137). The results of protocols using calcineurin inhibitor-sparing regimens are inconclusive, and no specific data are available regarding the bone-sparing effects of such strategies (133).
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Conclusions |
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TopAbstractIntroductionPathogenesis of Transplantation...ConclusionsReferences |
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In the past decade, the wider recognition of transplantation-related osteoporosis may have led to a decrease in the risk of fractures in the individual patient. Nonetheless, this progress may be offset by the rapid increase in the number of organs transplanted and the improved survival of transplant recipients, which ultimately puts a greater number of individuals at risk for transplantation-related osteoporosis. Even today, fracture rates remain unacceptably high, necessitating continued vigilance to address a common complication of organ transplantation.
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Footnotes |
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Abbreviations: BMD, Bone mineral density; CHF, congestive heart failure; CSA, cyclosporine A; ESRD, end-stage renal disease; FN, femoral neck; HPG, hypothalamic-pituitary-gonadal; LS, lumbar spine; 25-OHD, 25-hydroxyvitamin D.
Received October 6, 2004.
Accepted December 20, 2004.
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TopAbstractIntroductionPathogenesis of Transplantation...ConclusionsReferences |
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