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

Steven Boonen, Clifford Rosen, Roger Bouillon, Andreas Sommer, Malcolm McKay, David Rosen, Steven Adams, Paul Broos, Jan Lenaerts, Jef Raus, Dirk Vanderschueren, Piet Geusens
2002 Journal of Clinical Endocrinology and Metabolism  
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, placebocontrolled 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
more » ... continuous administration of either placebo (n ‫؍‬ 10), 0.5 mg/kg⅐d rhIGF-I/IGFBP-3 (n ‫؍‬ 9), or 1 mg/kg⅐d 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/kg⅐d) and 393 ng/ml (1 mg/ kg⅐d), 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 frac-ture surgery, patients treated with 1 mg/kg⅐d 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/kg⅐d 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. (J Clin Endocrinol Metab 87: 1593-1599, 2002) Abbreviations: BMD, Bone mineral density; IGFBP-3, IGF binding protein-3; OCA, osteocalcin; rhIGF, recombinant human IGF.
doi:10.1210/jcem.87.4.8426 pmid:11932288 fatcat:n4v3tb622vfmvg7bd7dzufkprm