title: Fracture risk in adult patients treated with growth hormone replacement therapy for growth hormone deficiency: a prospective observational cohort study.
abstract: BACKGROUND
  To our knowledge, no controlled studies of the effects of long-term growth hormone replacement on fracture risk in adult patients with growth hormone deficiency exist. We assessed the effect of growth hormone treatment on fracture risk in patients with growth hormone deficiency from the international Hypopituitary Control and Complications Study (HypoCCS) surveillance database.
  
  
  METHODS
  In this prospective cohort study, patients with growth hormone deficiency were analysed from the HypoCCS database of adults with hypopituitarism from the USA, Canada, Japan, and 14 European countries. Patients were eligible if they were aged 18 years or older and had an established diagnosis of growth hormone deficiency, either alone or with multiple pituitary hormone deficiencies, as identified by clinical history and biochemical testing. Patients were assessed over a mean follow-up period of 4·6 years (SD 3·8). The effect of growth hormone treatment on fracture risk was assessed by Cox proportional hazard modelling with adjustment for several confounders.
  
  
  RESULTS
  Between Jan 3, 1996, and Dec 15, 2012, we enrolled 10,673 patients to this study. Of the enrolled patients, 1032 patients were excluded from assessment because of incomplete data, leaving 9641 in the analysis cohort. Of these patients, 8374 of received growth hormone and 1267 did not. Annual fracture incidence rate was lower in patients who received growth hormone than in those who did not (fracture incidence rate 1·19% vs 1·91%, hazard ratio [HR] 0·69, 95% CI 0·54-0·88). However, no difference in fracture risk was observed between patients who did and did not receive growth hormone treatment in the subgroup of patients with pre-existing osteoporosis (n=826; 0·97, 0·48-1·95).
  
  
  CONCLUSIONS
  Our results suggest that growth hormone replacement therapy could be protective against fracture for adult patients with growth hormone deficiency without previously reported osteoporosis. Starting growth hormone therapy before the onset of osteoporosis might be optimum for bone health of adult patients with growth hormone deficiency.
  
  
  BACKGROUND
  Eli Lilly and Co.
authors: Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, IN, USA. Electronic address: moda@lilly.com.
authors: Daojun
authors: D
authors: Mo
authors: Northwest Pituitary Center, Departments of Medicine and Neurological Surgery, Oregon Health and Science University, Portland, OR, USA.
authors: Maria
authors: M
authors: Fleseriu
authors: Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, IN, USA.
authors: Rong
authors: R
authors: Qi
authors: Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, IN, USA.
authors: Nan
authors: N
authors: Jia
authors: Eli Lilly and Company, Lilly Research Laboratories, Windlesham, UK.
authors: Christopher Jeremy
authors: CJ
authors: Child
authors: Clinic and Laboratory of Endocrinology, Gasthuisberg, KU Leuven, Leuven, Belgium.
authors: Roger
authors: R
authors: Bouillon
authors: Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, IN, USA.
authors: Dana Sue
authors: DS
authors: Hardin
mesh_terms: D000328:Adult; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology* / Q000517:prevention & control; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D019382:Human Growth Hormone