Effects of 12 months of recombinant growth hormone therapy on parameters of bone metabolism and bone mineral density in patients on chronic hemodialysis

Background: Renal osteodystrophy is common in patients with chronic renal failure (CRF) on hemodialysis (HD), leading to reduced bone mineral density (BMD) and higher bone fracture incidences. Since growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are known to enhance bone metabolism and BMD, and CRF patients exhibit GH and IGF-1 resistance, recombinant human GH (rhGH) therapy could be beneficial for these patients. Methods: This study evaluated the effects of a 12-month rhGH therapy on bone metabolism parameters; alkaline phosphatase (AP), osteocalcin (OC), procollagen I carboxyterminal propeptide (PICP), telopeptide ICTP, serum crosslaps(TM), n-terminal propeptide of type III procollagen (PIIINP) and intact parathyroid hormone (iPTH), as well as on BMD of the lumbar spine and the femoral neck in 19 malnourished HD patients (10 females, 9 males) with a mean age of 59.3 +/- 13.4 yrs. Fourteen patients completed the 12-month study. RhGH (0.25 IU/kg) was given subcutaneously 3x/week after each dialysis session. Results: IGF-1 concentrations rose significantly from 169.2 +/- 95.6 to 262.9 +/- 144.4 ng/mL (p < 0.01) after 3 months, followed by a slight decline over the next 9 months. PICP as a bone formation marker significantly increased after 3 months from 250.1 +/- 112.6 to 478.5 +/- 235.2 ug/L (p < 0.01), as well as PIIINP, whereas OC and bone resorption parameters like ICTP showed only a slight increase (ICTP: 50.3 +/- 18.5 to 70.0 +/- 39.5 ug/L after 3 months (ns)). All bone metabolism parameters slightly declined in the following 9 months, but remained above baseline values after 12 months. PTH rose from 198.0 +/- 139.2 to 456.0 +/- 268.7 ng/ml, p < 0.01 after 6 months. BMD of the lumbar spine showed a significant reduction after 3-month rhGH therapy (0.80 +/- 0.17 vs. 0.77 +/- 0.16 g/cm(2), p < 0.01), but returned to baseline values after 12 months. BMD of the femoral neck remained stable during the entire study. Conclusions: In summary, 12-month rhGH treatment in patients on chronic HD caused a significant increase in IGF-1, together with an increase in bone turnover. In addition, there was a temporary reduction in BMD of the lumbar spine seen, which returned to baseline values after 12 months.