Back to Search
Start Over
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.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2002 Apr; Vol. 87 (4), pp. 1593-9. - Publication Year :
- 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 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.
- Subjects :
- Aged
Aged, 80 and over
Bone Density drug effects
Bone Remodeling drug effects
Double-Blind Method
Drug Combinations
Feasibility Studies
Female
Follow-Up Studies
Humans
Insulin-Like Growth Factor I adverse effects
Insulin-Like Growth Factor I analysis
Osteoporosis physiopathology
Pilot Projects
Placebos
Recombinant Proteins adverse effects
Recombinant Proteins therapeutic use
Femoral Fractures etiology
Insulin-Like Growth Factor Binding Protein 3 therapeutic use
Insulin-Like Growth Factor I therapeutic use
Muscle, Skeletal drug effects
Osteoporosis complications
Osteoporosis drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0021-972X
- Volume :
- 87
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 11932288
- Full Text :
- https://doi.org/10.1210/jcem.87.4.8426