This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Boonen, S. Articles by Geusens, P. Search for Related Content PubMed PubMed Citation Articles by Boonen, S. Articles by Geusens, P.

Musculoskeletal Effects of the Recombinant Human IGF-I/IGF Binding Protein-3 Complex in Osteoporotic Patients with Proximal Femoral Fracture: A Double-Blind, Placebo-Controlled Pilot Study

Katholieke Universiteit Leuven (S.B., R.B., P.B., D.V.), B-3000 Leuven, Belgium; University of Maine (C.R.), Bangor, Maine 04401; Celtrix Pharmaceuticals (A.S., M.M., D.R., S.A.), Santa Clara, California 95054; and Limburgs Universitair Centrum (J.L., J.R., P.G.), B-3590 Diepenbeek, Belgium

Address all correspondence and requests for reprints to: Steven Boonen, M.D., Ph.D., Leuven University Center for Metabolic Bone Diseases and Division of Geriatric Medicine, Katholieke Universiteit Leuven, University Hospitals K.U. Leuven, Brusselsestraat 69, B-3000 Leuven, Belgium. E-mail: . steven.boonen{at}uz.kuleuven.ac.be

Abstract

The administration of recombinant human IGF-I complexed with its predominant binding protein IGF binding protein-3 (rhIGF-I/IGFBP-3) may allow the safe administration of higher doses of IGF-I than can be accomplished with rhIGF-I alone. The aim of this randomized, double-blind, placebo- controlled pilot study was to evaluate the short-term safety and musculoskeletal effects of rhIGF-I/IGFBP-3 in older women (aged 65–90 yr) with recent hip fracture. Within 72 h after the event, 30 patients received continuous administration of either placebo (n = 10), 0.5 mg/kg·d rhIGF-I/IGFBP-3 (n = 9), or 1 mg/kg·d rhIGF-I/IGFBP-3 (n = 11). Treatment was administered by sc infusion through a portable mini-pump for a total of 8 wk after hip fracture surgery, with patient follow-up to 6 months after surgery. Efficacy evaluations included a contralateral hip bone density determination, markers of bone turnover (including serum osteocalcin and urinary excretion of N-telopeptide), grip strength, and tests of functional ability. During the administration of rhIGF-I/IGFBP-3, mean serum levels of IGF-I significantly (P < 0.001) increased from 83 ng/ml to 289 ng/ml (0.5 mg/kg·d) and 393 ng/ml (1 mg/kg·d), respectively. Both doses were well tolerated, and no hypoglycemia or other therapy-induced side effects were observed. After an initial loss of hip bone density after hip fracture surgery, patients treated with 1 mg/kg·d rhIGF-I/IGFBP-3 regained a substantial portion of their femoral bone mass. At 6 months postfracture (4 months after the 2-month infusion), they showed a statistically not significant decrease from baseline in hip bone density (-2.6%, P = 0.53). Placebo-treated patients, on the other hand, failed to regain lost bone: at 6 months postfracture, bone density in the placebo group had declined by 6.1% (P = 0.04). Additionally, in patients treated with 1.0 mg/kg·d rhIGF-I/IGFBP-3, grip strength had increased from baseline by 11.4% by the end of the study (P = 0.04) whereas patients on placebo lost 11.6% from baseline (P = 0.16). This increase in muscle strength in the high-dose group was associated with a positive effect on functional recovery. We conclude that a 2-month infusion of rhIGF-I/IGFBP-3 in patients with recent hip fracture is feasible, safe, and well tolerated. Analyzing the effects on bone mass, muscle strength, and functional ability, we observed beneficial trends. In the context of a small exploratory study, these findings should be interpreted with caution, but they support the need for future trials to further assess the therapeutic potential of rhIGF-I/IGFBP-3 in elderly subjects with osteoporosis.

This article has been cited by other articles:

				A. McDonald, R. M Williams, F. M Regan, R. K Semple, and D. B Dunger IGF-I treatment of insulin resistance Eur. J. Endocrinol., August 1, 2007; 157(suppl_1): S51 - S56. [Abstract] [Full Text] [PDF]

				T. Saukkonen, F. Shojaee-Moradie, R. M. Williams, R. Amin, K. C. Yuen, A. Watts, C. L. Acerini, A. M. Umpleby, and D. B. Dunger Effects of Recombinant Human IGF-I/IGF-Binding Protein-3 Complex on Glucose and Glycerol Metabolism in Type 1 Diabetes. Diabetes, August 1, 2006; 55(8): 2365 - 2370. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, J. N. Roemmich, E. J. Richmond, and C. Y. Bowers Somatotropic and Gonadotropic Axes Linkages in Infancy, Childhood, and the Puberty-Adult Transition Endocr. Rev., April 1, 2006; 27(2): 101 - 140. [Abstract] [Full Text] [PDF]

				C. Camacho-Hubner, S. Rose, M. A. Preece, M. Sleevi, H. L. Storr, F. Miraki-Moud, F. Minuto, J. Frystyk, A. Rogol, G. Allan, et al. Pharmacokinetic Studies of Recombinant Human Insulin-Like Growth Factor I (rhIGF-I)/rhIGF-Binding Protein-3 Complex Administered to Patients with Growth Hormone Insensitivity Syndrome J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1246 - 1253. [Abstract] [Full Text] [PDF]

				D. R. Clemmons, M. Sleevi, and W. H. Busby Jr. Recombinant, Nonglycosylated Human Insulin-Like Growth Factor-Binding Protein-3 (IGFBP-3) Is Degraded Preferentially after Administration to Type II Diabetics, Resulting in Increased Endogenous Glycosylated IGFBP-3 J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6561 - 6568. [Abstract] [Full Text] [PDF]

				T. Troosters, R. Casaburi, R. Gosselink, and M. Decramer Pulmonary Rehabilitation in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., July 1, 2005; 172(1): 19 - 38. [Full Text] [PDF]

				M. C. Kostek, M. J. Delmonico, J. B. Reichel, S. M. Roth, L. Douglass, R. E. Ferrell, and B. F. Hurley Muscle strength response to strength training is influenced by insulin-like growth factor 1 genotype in older adults J Appl Physiol, June 1, 2005; 98(6): 2147 - 2154. [Abstract] [Full Text] [PDF]

				L. E. Wehren, W. G. Hawkes, J. R. Hebel, D. L. Orwig, and J. Magaziner Bone Mineral Density, Soft Tissue Body Composition, Strength, and Functioning After Hip Fracture J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2005; 60(1): 80 - 84. [Abstract] [Full Text] [PDF]

				M. R. Hathaway, W. R. Dayton, M. E. White, and M. S. Pampusch Effects of antimicrobials and weaning on porcine serum insulin-like growth factor binding protein levels J Anim Sci, June 1, 2003; 81(6): 1456 - 1463. [Abstract] [Full Text] [PDF]