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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/2646

Title: 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
Authors: Boonen, S
Rosen, C
Bouillon, R
Sommer, A
McKay, M
Rosen, D
Adams, S.
Broos, P
Lenaerts, J
Vanderschueren, D
Issue Date: 2002
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 rhlGF-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 rhlGF-I/IGFBP-3 (n = 9), or 1 mg(kg.d rhIGF-I/IGFBP-3 (n = 11). Treatment was administered by se 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 rhlGF-I/IGFBP-3 in elderly subjects with osteoporosis.
Notes: Katholieke Univ Leuven, Ctr Metab Bone Dis, B-3000 Louvain, Belgium. Univ Maine, Bangor, ME 04401 USA. Celtrix Pharmaceut Inc, Santa Clara, CA 95054 USA. Limburgs Univ Ctr, B-3590 Diepenbeek, Belgium.Boonen, S, Katholieke Univ Leuven, Ctr Metab Bone Dis, Brusselsestr 69, B-3000 Louvain, Belgium.
URI: http://hdl.handle.net/1942/2646
Link to publication: http://jcem.endojournals.org/cgi/content/abstract/87/4/1593
ISI #: 000174963100027
ISSN: 0021-972X
Category: A1
Type: Journal Contribution
Validation: ecoom, 2003
Appears in Collections: Research publications

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