What is the pathophysiology of heart transplantation-related osteoporosis?

Updated: Jul 02, 2020
  • Author: Carmel M Fratianni, MD, FACE; Chief Editor: George T Griffing, MD  more...
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As with patients awaiting lung transplantation, only a minority of patients awaiting cardiac transplantation have normal bone density. Shane et al studied 101 patients with advanced congestive heart failure who were awaiting transplantation. Only 50% and 47% had normal BMD at the LS spine and total hip, respectively. [16]

The reasons for this are likely multifactorial. Patients with end-stage congestive heart failure are uniformly exposed to potent loop diuretics that promote negative calcium balance, and they often have coexisting renal disease and hepatic congestion from their low-flow state. Low serum concentrations of 25(OH) vitamin D and 1,25-dihydroxyvitamin D with secondary hyperparathyroidism are quite common. As the disease advances, patients become less mobile and have less sun exposure.

Not surprisingly, Shane et al found that vitamin D deficiency was significantly more common in the patients with more severe heart failure. [16] However, Iqbal et al did not find significantly low BMD in the lumbar spine and hip, relative to age and sex, in ambulatory patients with heart failure who were waiting for cardiac transplantation. [17]

Vertebral fractures are highly prevalent among cardiac transplant recipients, with a fracture prevalence of 18-50% reported across various series. [18] Among 47 patients monitored by Shane et al postcardiac transplant, 17 sustained 34 fractures after 1 year, despite having adequate calcium and vitamin D. At least 1 fracture was experienced by 54% of the women and 29% of the men. The vast majority (85%) of fractures occurred in the initial 6 months following transplantation, with most fractures involving the spine. Women with low femur-neck density were significantly more likely to sustain posttransplantation fractures. [19]

Following cardiac transplantation, LS spine bone density typically declines 6-10% in the first 6 months, after which it stabilizes. Hip density similarly declines in the first year, dropping 10-15% below pretransplant levels.

After the first year, bone loss usually slows, and LS spine density may actually increase slightly in the third year. [18] In comparison, after the second and third years following cardiac transplant, the one-third distal radius, a site enriched for cortical bone and susceptible to parathyroid hormone (PTH) action, shows evidence of continued bone loss. [18]

Since most bone mass is accrued by the late teenage years, concern exists whether patients who undergo transplant during these critical years would fail to accrue normal bone mass or delay achievement of peak bone mass. A cross-sectional case control study of 9 patients who were 12-16 years old at the time of cardiac transplantation found that at 8-16 years posttransplant, transplant recipients had shorter stature than calculated midparental height would predict. [20] Biochemical parameters suggested renal impairment with secondary hyperparathyroidism, without a difference in vitamin D levels between the treatment and control groups.

The authors suggest a pathogenic role for PTH in the osteoporosis in this population. Most of the patients received glucocorticoids at the time of study, yet glucocorticoids are usually associated with low bone turnover and suppressed bone formation. High bone turnover was noted in the study with markedly lower BMD at the forearm. Whether the increased bone turnover observed would ultimately be associated with ongoing loss of bone or continued bone growth was not clear from this cross-sectional study. [20]

In a noncontrolled report, the incorporation of mycophenolate mofetil in the immunosuppressant regimen has successfully reduced steroid requirements in a subset of patients with symptomatic osteoporosis after cardiac transplantation. However, in the small number (12) of patients studied, this did not result in an improvement of BMD after 1 year. [21]

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