What is the pathophysiology of lung transplantation-related osteoporosis?

Updated: Jul 02, 2020
  • Author: Carmel M Fratianni, MD, FACE; Chief Editor: George T Griffing, MD  more...
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Osteoporosis is very common among patients awaiting lung transplantation. Shane et al studied 70 patients awaiting transplant for end-stage lung disease and found osteoporosis in 30% at the lumbosacral (LS) spine and in 49% at the femur neck. Osteopenia (low bone mass) was noted at those sites in 35% and 31% of patients, respectively. [9] In other words, only a minority of patients awaiting transplant had normal bone density. Ferrari et al also prospectively evaluated changes in bone mass in 21 consecutive lung transplant candidates and confirmed this increased osteoporosis prevalence. [10] Prior to transplantation, BMD was decreased at all sites measured, and 35% of patients awaiting transplant had established osteoporosis, as defined by the World Health Organization (WHO).

Aris et al reported that nearly half (45%) of patients with end-stage lung disease awaiting transplant were at or below the fracture threshold. Moreover, following lung transplantation, nearly three quarters (73%) of patients were at or below the fracture threshold. [11] The prevalence rate of documented osteoporotic fractures was found to be 29% in patients with emphysema and 25% in patients with cystic fibrosis. Not surprisingly, the posttransplant BMD t- score was predicted by cumulative steroid dose.

Patients awaiting lung transplantation are at increased risk for osteoporosis because of the following:

  • Malnutrition

  • Unrecognized vitamin D deficiency

  • Tobacco use

  • Decreased mobility

  • Glucocorticoid exposure

Cystic fibrosis, a common indication for transplantation, is itself associated with low bone mass and fragility fractures because of (1) delayed puberty and hypogonadism and (2) chronic malnutrition with pancreatic insufficiency causing calcium and vitamin D malabsorption. Despite the common practice of giving supplemental oral vitamin D in patients with cystic fibrosis, the usual daily doses of 400-800 IU of vitamin D are often ineffective in maintaining normal vitamin D stores. Donovan et al found that 40% of patients with cystic fibrosis receiving that dosage of vitamin D were frankly vitamin D deficient. [12]

Shane et al noted vitamin D deficiency in 36% of patients with cystic fibrosis awaiting transplantation, although vitamin D deficiency was also very common among other patients with end-stage lung disease. [9] In this series, 20% of patients with chronic obstructive pulmonary disease awaiting transplant had vitamin D deficiency, which was associated with more severe demineralization at the LS spine and hip.

Significant glucocorticoid exposure is nearly universal in persons with end-stage lung disease. Israel et al reported that even inhaled corticosteroids lead to a dose-related decline in bone density at the hip. [13] Similarly, van Staa et al reported that vertebral, nonvertebral, and hip fractures occur with increased frequency in association with inhaled corticosteroids. [14] Note that only a very few patients receiving long-term glucocorticoid therapy in the study by Shane et al were simultaneously receiving an effective antiresorptive agent for osteoporosis prevention. [9, 15]

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