Relationship Between Immunosuppression and Osteoporosis in an Outpatient Liver Transplant Clinic

doi:10.1016/j.transproceed.2005.02.078

Transplantation Proceedings

Volume 37, Issue 4, May 2005, Pages 1910-1911

https://doi.org/10.1016/j.transproceed.2005.02.078 Get rights and content

Abstract

Background

The aim of this study is to determine the relationship between immunosuppression, disease state, and osteoporosis in an outpatient liver transplant clinic.

Methods

All liver transplant recipients visiting an outpatient transplant clinic received bone density scanning with a dual-energy X-ray absorptiometry (DEXA) device of the calcaneal bone after completing a questionnaire assessing risk and medications currently being used.

Results

Of the 137 liver transplant (OLT) recipients completing questionnaires and receiving DEXA screening, patients with low bone density (n = 50) were older (56.6 ± 12.7 years vs 50.2 ± 10.1 years; P = .02) compared with normal density patients (n = 87) and were predominantely female (64.0% vs 35.6%; P = .01). Based on disease state, patients with cholestatic liver failure had lower bone calcaneal area (17.3 ± 1.3 cm² vs 18.9 ± 1.57 cm²; P < .01). Patients taking tacrolimus (n = 112), as compared with cyclosporine (n = 25), had a tendency toward fewer findings of low bone density (37.5% [42 of 112] vs 56.0% [14 of 25]; P = .08) but had more risk factors (3.1 ± 1.2 vs 2.1 ± 0.8; P = .001) and a higher prednisone dose (4.4 ± 5.9 mg/d vs 2.1 ± 3.8 mg/d; P = .026). For patients weaned from prednisone, the tacrolimus patients were less likely to have low bone density (36.2% vs 68.8%; P = .02). Mycophenolate mofetil did not influence bone density or area measured.

Conclusions

After liver transplantation, patients taking cyclosporine were more likely to have low bone density compared with those taking tacrolimus.

Section snippets

Methods

In our liver transplant clinic, patients (n = 137) consented to participate in an IRB-approved study that evaluated their bone density as measured by bone mineral density (BMD), bone mineral content (BMC), bone area, as well as T scores, which is measured in relation to standard deviation from bone density in normal, young subjects. At the time of bone density screening, patients were asked to complete a questionnaire concerning risk factors such as family history, age, gender, postmenopausal

Results

Of the 137 patients screened, 50 (36.5%) had T scores inferring a high risk to develop osteopenia. Higher risk factors, as determined by questionnaire, correctly assessed lower bone densities (2.1 ± 1.4 vs 3.2 ± 1.7, P = .012). Lower bone densities, as expected, were associated with being female (35.6% [31 of 87] vs 64.0% [32 of 50], P = .01), with a difference seen in age of the groups (50.2 ± 10.1 years vs 56.5 ± 12.7 years, P = .02). When we looked at the impact primary disease had on bone

Discussion

From our study it appears that patients taking cyclosporine had a 1.90-fold increase in relative risk (RR) to develop osteopenia (RR = 1.90, 95% confidence interval RR [1.18, 3.05]). This increase in RR appears to be directly associated with cyclosporine, but not steroid dosing, risk factors, or disease state. The questionnaire used accurately assessed the risk of developing low bone density.

Although both steroids and cyclosporine appeared to be independent risk factors for developing lower

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Organ transplantation and osteoporosis
Curr Opin Rheumatol
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R.P. Sokhi et al.
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A.R. Bowman et al.
The role of testosterone in cyclosporine-induced osteopenia
J Bone Miner Res
(1997)

There are more references available in the full text version of this article.

Cited by (13)

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Transplant osteoporosis has become a prevalent problem, as the number of patients receiving organ transplants and posttransplant survival has increased. Transplant-related bone disease was initially thought to be predominantly related to glucocorticoids (GCs). However, even after the introduction of GC-sparing regimens, patients continued to sustain rapid bone loss and fractures. We now understand transplant osteoporosis to be a complex multifactorial disease. This chapter describes our current understanding of the effects of the most commonly prescribed immunosuppressive agents on bone and mineral metabolism, as well as potential effects of vitamin D on the immune system. The epidemiology, natural history, and pathogenesis of bone loss and fracture in organ transplant recipients are reviewed. The results of therapeutic trials are summarized and recommendations are provided for prevention of bone loss during the initial acute phase following organ transplantation, and treatment of established osteoporosis in organ transplantation patients.
Anti-osteoporosis effects of 1,4-dihydroxy-2-naphthoic acid in ovariectomized mice with increasing of bone density
2016, Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology
Citation Excerpt :
Osteoporosis has many causes, one of which is the administration of immunosuppressants following organ transplantation [19,20]. Similar to cyclosporine A, FK506 is classified as a T cell activity suppressor, and its administration increases osteoclasts under the condition of T cell activity suppression [30–32]. It is thought that the immune condition is changed by administration of FK506, and that RANKL expression on the extracellular surface of B cell membranes increases [33,34].
1,4-Dihydroxy-2-naphthoic acid (DHNA) is the main component of the metabolic products after fermentation by Propionibacterium freudenreichii ET-3. In this study, DHNA, vitamin K2 (VK2), and risedronate (Ris) were administered to ovariectomized (OVX) mice to ascertain their suppressive effects on bone mass reduction.
Fifty mice were divided into five groups: Sham, OVX, DHNA, VK2, and Ris groups. The drugs were administered daily for 8 weeks. Subsequently, blood was collected from the orbital venous plexus. The bilateral femurs and L5 lumbar vertebra were excised. To determine the effects of the drugs, we performed histomorphometric analyses of the left femur and L5 by micro-CT, biochemical analyses of serum samples, and histological analyses of the right femur.
The results for the total bone mineral density, bone volume density, trabecular thickness, trabecular number, trabecular separation, and histological analyses showed that bone resorption was improved in the DHNA and Ris groups compared with the OVX group. Furthermore, the biochemical analyses revealed that the production of inflammatory cytokines was suppressed in the DHNA and Ris groups.
The present findings show that DHNA suppresses the bone mass reduction in OVX mice, suggesting that it could be an alternative treatment for postmenopausal osteoporosis.
Osteoporosis in Organ Transplant Patients
2013, Osteoporosis: Fourth Edition
Transplant osteoporosis has become a prevalent problem, as the numbers of patients receiving organ transplants and post-transplant survival have increased. Transplant-related bone disease was initially thought to be predominantly related to glucocorticoids. However, even after the introduction of glucocorticoid-sparing regimens, patients continued to sustain rapid bone loss and fractures. We now understand transplant osteoporosis to be a complex multifactorial disease. This chapter describes our current understanding of the effects of the most commonly prescribed immunosuppressive agents on bone and mineral metabolism, as well as potential effects of vitamin D on the immune system. The epidemiology, natural history, and pathogenesis of bone loss and fracture in organ transplant recipients are reviewed. The results of therapeutic trials are summarized and recommendations are provided for prevention of bone loss during the initial acute phase following organ transplantation, and treatment of established osteoporosis in organ transplantation patients.
Effects of orthotopic liver transplantation in inbred rats on bone biomechanical properties
2010, Transplantation Proceedings
Citation Excerpt :
Although no significant change in the stiffness and energy absorption was observed, a definite downward trend was noticed among the OLT group (Table 4). The use of immunosuppressive drugs and the underlying liver disease are usually considered to be the major contributors to the high rate of posttransplant fracture.2,5,6,18 To ensure that the only factor damaging bone biomechanical properties is the OLT itself in our present study, we performed OLT in normal inbred rats rendering immunosuppression unnecessary, thereby excluding the effects of these drugs and of liver disease.
To determine the effects of orthotopic liver transplantation in inbred rats on the mechanical properties of bones at different anatomic sites.
The 24 rats that survived liver transplantation were paired with sham-operated rats of similar body weight. Six months after surgery, the lumbar vertebra, the proximal femur, and the middle femoral shaft were measured for their biomechanical properties and bone mineral density.
The ultimate force, the ultimate stress, the Young modulus and the bone mineral density of both the proximal femur and the middle femur shaft of the rats were significantly reduced in the liver transplant group. However, no significant change was observed in the various parameters that indicate the biomechanical properties and the bone mineral density of the lumbar vertebra.
Orthotopic liver transplantation impairs the biomechanical properties of the proximal femur and the middle femoral shaft. Orthotopic liver transplantation itself is one of the risk factors for posttransplant fracture.
Osteoporosis and solid organ transplantation
2007, Endocrinologia y Nutricion
El trasplante de órgano sólido se ha establecido como una opción importante para el tratamiento de muchas enfermedades. La osteoporosis es una complicación común tras un trasplante de órgano sólido y está relacionada con un incremento en la incidencia de fracturas y de la morbilidad en los receptores del trasplante. En esta presentación se pretende revisar los factores implicados en la patogenia de esta importante complicación, así como la evaluación, la prevención y las opciones posibles de tratamiento en la osteoporosis postrasplante.
Solid organ transplantation has become an established treatment option for many diseases. Osteoporosis is a common complication after solid organ transplantation and is associated with an increased incidence of fractures and related morbidity in transplant recipients. The present article reviews the factors contributing to the pathogenesis of this serious complication. The evaluation and prevention of post-transplantation osteoporosis, as well as the available treatment options, are also discussed.
Post-Transplantation Osteoporosis
2007, Endocrinology and Metabolism Clinics of North America
Citation Excerpt :
Several studies have suggested potential risk factors for bone loss and fracture following liver transplantation. Female gender and higher GC dose were associated with lower BMD in cross-sectional [55] and retrospective studies [56]. Whether the type of underlying liver disease predicts bone loss and fracture is controversial.
Osteoporosis is prevalent in transplant recipients and is related to pre- and post-transplantation factors. Low bone density and fractures may antedate transplantation, related to traditional risk factors for osteoporosis, effects of chronic illness, and end-stage organ failure and its therapy, on the skeleton. Bone loss after transplantation is related to adverse effects of immunosuppressive drugs (glucocorticoids and calcineurin inhibitors) on bone remodeling. Newer immunosuppressive medications may permit lower doses of glucocorticoids and may be associated with decreased bone loss and fractures. Bisphosphonates are currently the most effective agents for the prevention and treatment of post-transplantation osteoporosis.

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Clinical toxicities of immunosuppressantsOther toxicityRelationship Between Immunosuppression and Osteoporosis in an Outpatient Liver Transplant Clinic

Abstract

Background

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Organ transplantation and osteoporosis

Curr Opin Rheumatol

Bone mineral density among cirrhotic patients awaiting liver transplantation

Liver Transplant

The role of testosterone in cyclosporine-induced osteopenia

J Bone Miner Res

Clinical toxicities of immunosuppressants
Other toxicity
Relationship Between Immunosuppression and Osteoporosis in an Outpatient Liver Transplant Clinic