Mecasermin: new drug. Insufficient improvement in statural growth.

(1) Human insulin-like growth factor type 1 (IGF-1) is the main effector of growth hormone action. Primary IGF-1 deficiency is a rare disease, mainly resulting in very short stature; (2) Mecasermin is a recombinant IGF-1 marketed for this indication as a twice daily subcutaneous injection; (3) Clinical evaluation is mainly based on a non-comparative follow-up study of 76 children with an average age of 7 years, some of whom were treated for 8 years. The mean height at treatment initiation was 6.7 standard deviations below normal. Eight years later, it was 5.2 standard deviations below normal, i.e. their growth failure remained very severe; (4) The main short-term adverse effects of mecasermin are hypoglycaemia, headache and intracranial hypertension. Nearly one in 5 children developed tonsillar hypertrophy, resulting in otitis and hypoacusis; (5) Animal studies showed hypertrophy of other organs (kidneys, spleen and heart) as well as carcinogenic effects. The risk in humans is unknown; (6) The mecasermin packaging is not well-adapted (a multidose vial designed to be punctured several times), and is a potential source of contamination and errors. Prefilled pens or syringes would be easier to use; (7) In practice, the limited clinical benefits of mecasermin do not justify exposure to its potential risks.

Soy isoflavones do not modulate circulating insulin-like growth factor concentrations in an older population in an intervention trial.

Insulin-like growth factors (IGF) are essential for normal growth and maintenance of lean muscle mass; however, high insulin-like growth factor-I (IGF-I) and low IGF binding protein-3 (IGFBP-3) levels are also associated with several cancers. To test the hypothesis that long-term soy isoflavone supplementation decreases circulating IGF-I concentrations, we conducted a controlled, parallel-arm, double-blind intervention study with 150 participants (85% men), 50-80 y old. Participants were randomly assigned to consume a soy beverage powder daily for 12 mo. The active treatment group (+ISO) received soy protein containing 83 mg isoflavones, whereas the comparison group (-ISO) received soy protein containing 3 mg isoflavones. Serum IGF-I and IGFBP-3 were measured by ELISA. Mean change in serum IGF-I concentrations was similar in the two groups (+1.4 nmol/L in +ISO, +1.2 nmol/L in -ISO; P = 0.74, 95% confidence interval -1.1, +1.5 nmol/L for the 0.21 nmol/L difference between groups), indicating no effect of the isoflavone intervention. Similarly, the changes in IGFBP-3 and the IGF-I/IGFBP-3 ratio were similar in both groups, again showing no effect of +ISO treatment. A 12 mo, 83 mg/d soy isoflavone intervention did not modulate serum IGF in an older, mostly male population.

Estrogen protection against bone resorbing effects of parathyroid hormone infusion. Assessment by use of biochemical markers.

OBJECTIVE: Because parathyroid hormone (PTH) stimulates bone resorption, resistance to its actions might help maintain bone mass. We tested the hypothesis that the effects of estrogen on bone are accomplished in part by decreasing the sensitivity of the skeleton to the resorbing effects of PTH. STUDY DESIGN: Comparison of response to PTH infusion in untreated and estrogen-treated postmenopausal women with osteoporosis. INTERVENTION: (1-34) human PTH, 0.55 U/(kg.h), was infused intravenously over 20 hours. SETTING: The inpatient clinical research unit of a referral hospital. PATIENTS: Women with primary postmenopausal osteoporosis who were untreated (n = 15) or treated with estrogen (n = 17). MAIN OUTCOME MEASURES: Skeletal turnover indices including hydroxyproline, deoxypyridinoline, pyridinoline, tartrate-resistant acid phosphatase, alkaline phosphatase, bone Gla protein, and insulin-like growth factor-1. RESULTS: All basal indices were higher in untreated than in estrogen-treated women, but statistical differences were seen only for deoxypyridinoline and pyridinoline. During the 20-hour infusion, hydroxyproline/creatinine increased 0.023 mumol/mumol in untreated women but only 0.010 mumol/mumol in estrogen-treated women (P < 0.05). Corresponding changes for deoxypyridinoline/creatinine were 14.6 mumol/mumol and 3.5 mumol/mumol (P = 0.06). Tartrate-resistant acid phosphatase and pyridinoline increased only in untreated group. A circadian rhythm in circulating bone Gla protein was seen in both groups without clear PTH-induced effects or differences between groups. Alkaline phosphatase levels decreased and insulin-like growth factor-1 levels increased in both groups with no distinction between untreated and estrogen-treated women [corrected]. CONCLUSION: The estrogenized postmenopausal osteoporotic skeleton is less sensitive to the bone resorbing effects of acutely administered PTH. There are no differential effects on bone formation.