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, 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/cm2, 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.
Kotzmann
Harald
H
Division of Endocrinology and Metabolism, Department of Medicine III, Ludwig Boltzmann Institute for Experimental Endocrinology, University of Vienna, Vienna, Austria. harald.kotzmann@utanet.at
Riedl
Michaela
M
Pietschmann
Peter
P
Schmidt
Alice
A
Schuster
Ernst
E
Kreuzer
Sören
S
Kainberger
Franz
F
Frisch
Herwig
H
Geyer
Georg
G
Hörl
Walter H
WH
Mayer
Gert
G
Luger
Anton
A
D015502:Absorptiometry, Photon; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism*; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000378:metabolism / Q000517:prevention & control; D024042:Collagen Type I; D004311:Double-Blind Method; D005260:Female; D005272:Femur Neck / Q000378:metabolism; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism / Q000628:therapy; D008159:Lumbar Vertebrae / Q000378:metabolism; D008297:Male; D044342:Malnutrition / Q000150:complications / Q000175:diagnosis / Q000378:metabolism; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides; D011347:Procollagen / Q000097:blood; D006435:Renal Dialysis / Q000009:adverse effects
D024042:Collagen Type I; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C041876:procollagen Type III-N-terminal peptide; C042813:procollagen type I carboxy terminal peptide; D015675:Osteocalcin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I