title: The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture.
abstract: OBJECTIVE
  To evaluate the effects of MK-0677, an orally active growth hormone (GH) secretagogue, on functional recovery from hip fracture in previously mobile older individuals.
  
  
  METHODS
  Placebo-controlled, randomized, double-blind trial.
  
  
  METHODS
  Thirteen medical centers in England, Sweden, Denmark, Belgium, Switzerland, Canada, and the United States. Patients were recruited between 3 and 14 days postoperatively, or no more than 18 days postfracture, at acute care hospitals and rehabilitation centers.
  
  
  METHODS
  One hundred sixty-one hip-fracture patients were enrolled. Entry criteria included consenting hip-fracture patients who were aged 65 and older and who were ambulatory before their fracture, medically stable postoperatively, and mentally competent. Patients were excluded if they had multiple fractures or severe trauma, diabetes mellitus, cancer, uncontrolled hypertension, congestive heart failure, or total hip replacement in the involved extremity.
  
  
  METHODS
  Random assignment to 6 months of daily treatment with MK-0677 or placebo. Patients were followed for an additional 6 months after completion of therapy.
  
  
  METHODS
  Change from Week 6 to Week 26 in a panel of functional performance measures. Additional outcome measures included change in the Sickness Impact Profile for Nursing Homes (SIP-NH), the ability to live independently, and insulin-like growth factor I (IGF-I) levels.
  
  
  RESULTS
  MK-0677 treatment increased serum IGF-I levels by 84% (95% confidence interval (CI)=63-107), compared with an increase of 17% (95% CI=8-28) on placebo. There were no significant differences between MK-0677 and placebo in improvement in functional performance measures or in the overall SIP-NH score. Although MK-0677 patients showed greater improvement relative to placebo in three of four lower extremity functional performance measures, in the physical domain of the SIP, and in the ability to live independently, these differences were not statistically significant.
  
  
  CONCLUSIONS
  Although MK-0677 treatment increased serum IGF-I, it is uncertain whether clinically significant effects on physical function were achieved. Measuring function in clinical trials in hip-fracture patients is difficult because of the lack of validated outcome measures, high variability, and the lack of a baseline assessment. Present functional performance measures may not be sufficiently responsive for use as the primary endpoint of small intervention studies; alternatively, stimulation of GH may not result in significant functional improvement.
authors.affiliation: Merck Research Laboratories, Rahway, New Jersey, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Bach
authors.forename: Kenneth
authors.initials: K
authors.lastname: Rockwood
authors.forename: Carl
authors.initials: C
authors.lastname: Zetterberg
authors.forename: Gorm
authors.initials: G
authors.lastname: Thamsborg
authors.forename: Réjean
authors.initials: R
authors.lastname: Hébert
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Devogelaer
authors.forename: Jens Sandahl
authors.initials: JS
authors.lastname: Christiansen
authors.forename: René
authors.initials: R
authors.lastname: Rizzoli
authors.forename: J Lockwood
authors.initials: JL
authors.lastname: Ochsner
authors.forename: Norman
authors.initials: N
authors.lastname: Beisaw
authors.forename: Oscar
authors.initials: O
authors.lastname: Gluck
authors.forename: Leisure
authors.initials: L
authors.lastname: Yu
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwab
authors.forename: Jeanne
authors.initials: J
authors.lastname: Farrington
authors.forename: Alice M
authors.initials: AM
authors.lastname: Taylor
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ng
authors.forename: Vivian
authors.initials: V
authors.lastname: Fuh
mesh_terms: D000203:Activities of Daily Living; D000284:Administration, Oral; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D015577:Geriatric Assessment; D005947:Glucose / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006620:Hip Fractures / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology / Q000534:rehabilitation; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D016743:Mental Competency; D020127:Recovery of Function; D012449:Safety; D018434:Sickness Impact Profile; D013141:Spiro Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D005947:Glucose; D006442:Glycated Hemoglobin; D007211:Indoles; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D013141:Spiro Compounds; C094817:ibutamoren mesylate