Organ transplantation and osteoporosis

Epstein, Sol; Shane, Elizabeth; Bilezikian, John P.

doi:10.1097/00002281-199505000-00018

Cited by 102 publications

(47 citation statements)

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“…With such specificity, one would expect that the skeletal effects of calcineurin inhibition by FK506 and calcineurin gene deletion are identical. In other words, reduced osteoblast differentiation and bone formation should be the mechanism through which calcineurin inhibitors cause bone loss (18)(19)(20)(21). Although this may be the case, the osteoporosis resulting from calcineurin inhibitors is characterized by a high-turnover state in which both bone resorption and through-coupling bone formation are elevated (18,19).…”

Section: Discussionmentioning

confidence: 99%

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Calcineurin regulates bone formation by the osteoblast

Sun

Blair

Peng

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

144

107

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Two of the most commonly used immunosuppressants, cyclosporine A and tacrolimus (FK506), inhibit the activity of a ubiquitously expressed Ca 2؉ ͞calmodulin-sensitive phosphatase, calcineurin. Because both drugs also cause profound bone loss in humans and in animal models, we explored whether calcineurin played a role in regulating skeletal remodeling. We found that osteoblasts contained mRNA and protein for all isoforms of calcineurin A and B. TAT-assisted transduction of fusion protein TAT-calcineurin A␣ into osteoblasts resulted in the enhanced expression of the osteoblast differentiation markers Runx-2, alkaline phosphatase, bone sialoprotein, and osteocalcin. This expression was associated with a dramatic enhancement of bone formation in intact calvarial cultures. Calcineurin A␣ ؊/؊ mice displayed severe osteoporosis, markedly reduced mineral apposition rates, and attenuated colony formation in 10-day ex vivo stromal cell cultures. The latter was associated with significant reductions in Runx2, bone sialoprotein, and osteocalcin expression, paralleled by similar decreases in response to FK506. Together, the gain-and loss-of-function experiments indicate that calcineurin regulates bone formation through an effect on osteoblast differentiation.FK506 ͉ osteoporosis ͉ runx-2

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Section: Discussionmentioning

confidence: 99%

“…The systemic administration of either drug to rats causes a dramatic osteoporosis (18,19). In humans, acute, rapid, severe bone loss ensues with a fracture incidence approaching 65% (20,21). It has been speculated, but never proven in either animals or humans, that cyclosporine A or FK506 use the calcineurin pathway to exert their skeletal effects.…”

mentioning

confidence: 99%

Calcineurin regulates bone formation by the osteoblast

Sun

Blair

Peng

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

144

107

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“…Glucocorticoid [26][27][28][29][30][31][32][33][34][35] and methotrexate [36][37][38][39] treatment and cranial irradiation [40][41][42] have been inconsistently associated with the risk of osteopenia. However, findings of these studies have been limited by the generally small and heterogeneously treated patient cohorts.…”

Section: 425mentioning

confidence: 99%

Bone mineral density and osteonecrosis in survivors of childhood allogeneic bone marrow transplantation

Kaste

Shidler

Tong

et al. 2004

Bone Marrow Transplant

108

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Summary:Our purpose was to evaluate frequency and severity of bone mineral decrements and frequency of osteonecrosis in survivors of pediatric allogeneic bone marrow transplantation (alloBMT). We retrospectively reviewed demographic information, treatment, magnetic resonance (MR) imaging studies (hips and knees), and bone mineral density (BMD) studies of 48 patients as measured by quantitative computed tomography (QCT). In all, 24 patients were male; 37 were Caucasian. Median age at alloBMT was 10.3 years (1.6-20.4 years). Of the 48 patients, 43 underwent QCT. Median time between alloBMT and imaging was 5.1 years (1.0-10.2 years). Median BMD Z-score was À0.89 (À4.06 to 3.05). BMD Z-score tended to be associated with female sex (P ¼ 0.0559) but not with age at BMT, race, primary diagnosis, time from alloBMT, T-cell depletion of graft, total-body irradiation, or acute/chronic graft-versus-host disease (GVHD). MR showed osteonecrosis in 19 of 43 (44%). We found no associations between osteonecrosis and sex, race, diagnosis, age at BMT, history of GVHD, time from BMT, or T-cell depletion. Seven patients (15%) had MR changes of osteonecrosis and BMD Z-scores of less than -1 s.d. We conclude that pediatric alloBMT survivors have decreased BMD and are at risk of osteonecrosis. They should be monitored to assure early intervention that may ameliorate adverse outcomes.

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“…Following transplantation, use of chronic immunosuppression continues to cause osteoporosis [10][11]. Therefore, spontaneous fractures or tend to easy fracture are expected following all solid organ transplantations [11][12][13][14].…”

Section: Discussionmentioning

confidence: 99%

Trauma to transplanted kidney with open fractures: Report of a case

et al. 2010

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AbstractA 45 year-old man, who had undergone kidney transplantation 7 years prior, was admitted to hospital after a motorcycle accident. The patient was conscious, hemodynamically stable, and had suffered open tibia and femur fractures, as well as closed pubic arm fractures. He had gross hematuria and radiologic study revealed a 3.5 cm length laceration on the transplanted kidney. His renal functions and hematuria recovered after intensive care. He required 2 surgeries for the open fractures but his general condition worsened after the surgical interventions. Acinetobacter, Candida albicans and pseudomonas aeruginosa were determined by blood cultures. Immunosupressive drugs (cyclosporine, prednisolone and azathioprine) were stopped. Despite intensive care, the patient died of sepsis 17 days post trauma. Open fractures of long bones provide a higher risk of sepsis in transplant patients than closed fractures.

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Organ transplantation and osteoporosis

Cited by 102 publications

References 0 publications

Calcineurin regulates bone formation by the osteoblast

Calcineurin regulates bone formation by the osteoblast

Bone mineral density and osteonecrosis in survivors of childhood allogeneic bone marrow transplantation

Trauma to transplanted kidney with open fractures: Report of a case

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