Hyperparathyroidism and long-term bone loss after renal transplantation

Background: While early bone loss after renal transplantation (RT) is well described, factors affecting the long-term fate of bone have received less attention. Methods: Whole body (WB), lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) was measured using dual energy X-ray absorptionometry in 126 stable RT patients and repeated in 114 survivors after 3 yr. Percentage change per year (%/yr) was correlated to clinical and biochemical markers of bone metabolism. Results: Low bone mass was a marker of increased mortality (FN<80% normal 6.3%/yr; >80% 2.2%/yr). Percent change was WB -0.7+/-1.5 (p<0.01); LS -0.3+/-2.6; FN -1.0+/-3.0 (p<0.01) and, corrected for expected loss for age and sex: WB -0.5 (p<0.01); LS 0.0; FN-0.8 (p<0.05). Factors associated with increased loss rates were (LS%): short RT duration [<2 yr: -3.1 (p<0.01)], high prednisone dose [>9 mg/d:-1.9 (p<0.01)], high cyclosporine trough concentration [>175 ng/L: -1.9 (p<0.05)], high hyperparathyroidism (PTH) [>150 ng/L: -1.5 (p<0.05)], high alkaline phosphatase [>275 U/L: -1.6 (p<0.05)], high osteocalcin [>75 mug/L: -1.6 (p<0.05)]. Marginal detrimental effects of uremia, hypoalbuminemia and hyperphosphatemia were noted. Thiazide treatment seemed to protect against, and furosemide to exacerbate, bone loss, but this may have been related to associated uremia. Patients treated with vitamin D gained bone, while untreated patients with low initial 1,25-dihydroxyvitamin D lost bone [FN%-2.1 (p<0.05)]. The prevalence of PTH (52%) and hypercalcemia (22%) remained unchanged. There was no effect of sex hormone levels, calcium and phosphate excretion, or serum calcium. Conclusion: While LS BMD stabilizes after RT, there is a continuing loss of WB and FN BMD. The major causes of bone loss are steroid therapy and continuing PTH, with no tendency towards spontaneous resolution. Increased vitamin D and calcium therapy should be considered for this patient group, and more aggressive therapy, e.g. parathyroidectomy given for patients with resistant PTH of >150 ng/L.