Currently used growth-promoting treatment of children results in normal bone mass and density. A prospective trial of discontinuing growth hormone treatment in adolescents.
OBJECTIVE
The need for continued GH replacement in patients with childhood-onset GH deficiency (GHD) into adulthood has been recognized. The consequences of discontinuing GH treatment on bone mineralization in adolescent patients with GHD and short stature were examined over a period of 2 years.


METHODS
Forty adolescents (aged 16-21 years) treated with GH for more than 3 years and 16 closely matched healthy controls were studied. After a baseline visit, GH treatment was discontinued. The patients were then re-examined with the same protocol after 1 and 2 years. Twenty-one patients had continuing severe GHD into adulthood, while 19 patients were regarded as having sufficient endogenous GH secretion (GHS).


RESULTS
At baseline, there were no differences between the groups in total bone mineral content (BMC) or bone mineral density (BMD). After 2 years without GH treatment, BMC increased similarly in the GHD and GHS groups. BMC of the lumbar spine (L2-L4) increased only in the GHD group. Lumbar spine BMD increased in the GHD and the GHS groups. No changes were observed in the femoral neck region. Biochemical measurements showed that carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) and bone specific alkaline phosphates (ALP) were higher in the GHD and GHS groups at baseline compared with controls. Osteocalcin, carboxy-terminal propeptide of type I procollagen (PICP), ICTP and ALP decreased during the 2 years off treatment in both the GHD and GHS groups. PICP was also lower after 2 years in the GHD group compared with both the GHS group and controls.


CONCLUSIONS
After discontinuation of GH therapy in adolescents at or near final height, there was a continued increase in BMC and BMD both for adolescents with growth hormone deficiency and for those classified as growth hormone sufficient. These groups did not differ from controls at baseline or after 2 years. In the growth hormone deficiency group, biochemical markers for bone formation decreased to levels below those in the growth hormone sufficient and healthy control groups. Although the number of patients and controls in this study were small, the results indicate that the present treatment of Swedish GH-deficient children to final height results in normal BMD.
Fors
H
H
Göteborg Paediatric Growth Research Center, Sahlgrenska University Hospital, Sweden. hans.fors@vgregion.se
Bjarnason
R
R
Wirént
L
L
Albertsson-Wikland
K
K
Bosaeust
L
L
Bengtsson
B A
BA
Johannsson
G
G
D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001827:Body Height; D015519:Bone Density / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D016022:Case-Control Studies; D024042:Collagen Type I; D004334:Drug Administration Schedule; D005260:Female; D005272:Femur Neck; D006130:Growth Disorders / Q000097:blood / Q000188:drug therapy*; D013006:Growth Hormone / Q000008:administration & dosage* / Q000097:blood / Q000172:deficiency*; D006801:Humans; D008159:Lumbar Vertebrae; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000032:analysis; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides; D011347:Procollagen / Q000097:blood; D011446:Prospective Studies
D015415:Biomarkers; D024042:Collagen Type I; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C042813:procollagen type I carboxy terminal peptide; D015675:Osteocalcin; D013006:Growth Hormone; D000469:Alkaline Phosphatase; D002118:Calcium