What is the role of glucocorticoids in the pathogenesis of organ transplantation-related osteoporosis?

Updated: Jul 02, 2020
  • Author: Carmel M Fratianni, MD, FACE; Chief Editor: George T Griffing, MD  more...
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Answer

Answer

While a detailed discussion on glucocorticoid-induced bone loss is beyond the scope of this article, glucocorticoids are known to induce osteoporosis. An increased risk of vertebral fracture has been associated with an oral dose of prednisolone of as low as 2.5 mg/d, which is approximately equipotent to prednisone at 2.5 mg/d. Glucocorticoids are commonly prescribed in high doses, up to 120 mg of prednisone or its equivalent daily during periods of acute rejection and immediately posttransplantation.

Glucocorticoids promote bone loss through a variety of simultaneously operating mechanisms, as follows:

  • Reduce GI calcium absorption

  • Increase urinary calcium excretion

  • Induce secondary hyperparathyroidism

  • Decrease production of skeletal growth factors

  • Decrease the responsiveness of luteinizing hormone (LH) to gonadotropin-releasing hormone, thereby decreasing gonadal hormone production; may also directly decrease gonadal hormone production

  • Suppress corticotropin, thereby suppressing the adrenal production of androstenedione, a substrate for both testosterone and estrone production

  • Decrease osteoblast-mediated bone formation

  • Increase bone resorption

Glucocorticoids result in a disproportionate loss of cancellous or trabecular bone, possibly because trabecular bone has an inherently greater rate of turnover than cortical bone. Serum bone GLA protein, osteocalcin, is also inhibited. Thus, glucocorticoids induce a low-turnover osteopenia and disproportionately affect trabecular bone. [53]

With the advent of the cyclosporines in the early 1980s, graft survival markedly improved owing to decreased organ rejection. The introduction of cyclosporines allowed steroid doses to be substantially reduced. At the time, the hope was that the harmful effects of immunosuppression on the skeleton would be ameliorated. Unfortunately, this was not the case. The lowest effective dose of glucocorticoids is recommended to minimize loss of bone mass and risk of osteonecrosis (a common complication in the first 2 years following transplant).


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