Objectives: 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.
Design: Placebo-controlled, randomized, double-blind trial.
Setting: 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.
Participants: 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.
Intervention: 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.
Measurements: 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.
Conclusion: 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.
Ethans Karen D., MacKnight Chris, Hip fracture in the elderly : An interdisciplinary team approach to rehabilitation, 10.3810/pgm.1998.01.277
Marottoli Richard A., Berkman Lisa F., Cooney Leo M., Decline in Physical Function following Hip Fracture, 10.1111/j.1532-5415.1992.tb01980.x
Baudois, A two-year follow-up study, 18, 149S (1996)
Magaziner, A prospective study, 45, M101 (1990)
Leibson, A population-based study, 50, 1644 (2002)
Kramer, A comparison of rehabilitation settings, 277, 396 (1997)
Langlois Jean A., Maggi Stefania, Harris Tamara, Simonsick Eleanor M., Ferrucci Luigi, Pavan Mara, Sartori Leonardo, Enzi Giuliano, Self-Report of Difficulty in Performing Functional Activities Identifies a Broad Range of Disability in Old Age, 10.1111/j.1532-5415.1996.tb04065.x
Magaziner J., Hawkes W., Hebel J. R., Zimmerman S. I., Fox K. M., Dolan M., Felsenthal G., Kenzora J., Recovery From Hip Fracture in Eight Areas of Function, 10.1093/gerona/55.9.m498
Zadik, J Clin Endocrinol Metab, 60, 513 (1985)
Nonaka, Int J Sports Med, 18, S292 (1997)
Rudman, N Engl J Med, 323, 1 (1990)
Hennessey, J Am Geriatr Soc, 49, 852 (2001)
Hubbard, Rev Clin Gerontol, 12, 145 (2002)
Van der Lely, Eur J Endocrinol, 143, 585 (2000)
Patchett, A potent, orally active growth hormone secretagogue, 92, 7001 (1995)
Folstein, J Psychiatr Res, 12, 189 (1975)
Gerety M. B., Cornell J. E., Mulrow C. D., Tuley M., Hazuda H. P., Lichtenstein M., Aguilar C., Kadri A. A., Rosenberg J., The Sickness Impact Profile for Nursing Homes (SIP-NH), 10.1093/geronj/49.1.m2
Fox, Arch Phys Med Rehab, 77, 171 (1998)
Guralnik J. M., Simonsick E. M., Ferrucci L., Glynn R. J., Berkman L. F., Blazer D. G., Scherr P. A., Wallace R. B., A Short Physical Performance Battery Assessing Lower Extremity Function: Association With Self-Reported Disability and Prediction of Mortality and Nursing Home Admission, 10.1093/geronj/49.2.m85
Jette, Arch Phys Med Rehabil, 61, 395 (1980)
Reuben David B., Siu Albert L., An Objective Measure of Physical Function of Elderly Outpatients : The Physical Performance Test, 10.1111/j.1532-5415.1990.tb01373.x
Binder, Results of a randomized, controlled trial, 50, 1921 (2002)
O'Brien, Biometrics, 40, 1079 (1984)
Cohen, Statistical Power Analysis for the Social Sciences (1998)
Rockwood, J Clin Epidemiol, 46, 1113 (1993)
Stadnyk, J Clin Epidemiol, 51, 827 (1998)
JAGLAL SUSAN, LAKHANI ZUBAIR, SCHATZKER JOSEPH, Reliability, Validity, and Responsiveness of the Lower Extremity Measure for Patients with a Hip Fracture* : , 10.2106/00004623-200007000-00007
Liu, J Clin Endocrinol Metab, 87, 3125 (2002)
Marcantonio Edward R., Flacker Jonathan M., Michaels Mary, Resnick Neil M., Delirium Is Independently Associated with Poor Functional Recovery After Hip Fracture, 10.1111/j.1532-5415.2000.tb04718.x
Lindesay, Delirium in Old Age, 27 (2002)
Magaziner, Am J Public Health, 79, 274 (1989)
Broos, Int Surg, 74, 191 (1989)
Rasmussen, Breast Cancer Res Treat, 47, 219 (1998)
Yee, Breast Cancer Res Treat, 47, 197 (1998)
Surmacz, Breast Cancer Res Treat, 47, 255 (1998)
Oates, Breast Cancer Res Treat, 47, 269 (1998)
Huynh, Cancer Res, 58, 215 (1998)
Zuckerman, Clin Orthoped Rel Res, 274, 213 (1992)
Ogilvie-Harris, J Orthop Trauma, 7, 428 (1993)
Bonjour, Bone, 18, 139S (1996)
Schurch Marc-Andre, Protein Supplements Increase Serum Insulin-Like Growth Factor-I Levels and Attenuate Proximal Femur Bone Loss in Patients with Recent Hip Fracture : A Randomized, Double-Blind, Placebo-Controlled Trial, 10.7326/0003-4819-128-10-199805150-00002
Rockwood, Drugs Aging, 17, 295 (2000)
MacKnight, J Clin Epidemiol, 53, 1242 (2000)
Bibliographic reference
Bach, MA ; Rockwood, K ; Zetterberg, C ; Thamsborg, G ; Hebert, R ; et. al. The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture. In: Journal of the American Geriatrics Society, Vol. 52, no. 4, p. 516-523 (2004)