Treating a Patient with the Werner Syndrome and Osteoporosis Using Recombinant Human Insulin-like Growth Factor

1 November 1994 | Volume 121 Issue 9 | Pages 665-668

Objective: To assess the safety and effect of recombinant human insulin-like growth factor 1 (rhIGF-1) on measures of bone metabolism in a human model of age-related osteoporosis.

Design: 6-month prospective case study.

Setting: General clinical research center.

Patients: 1 patient with the Werner syndrome, a low serum IGF-1 level, and osteoporosis.

Intervention: Daily subcutaneous administration of rhIGF-1 for 6 months.

Measurements: Serum alkaline phosphatase, osteocalcin, type I procollagen C-peptide and urinary hydroxyproline, calcium, and pyridinoline cross-links as measures of bone metabolism and radial shaft, femoral neck, and lumbar bone masses.

Results: Serum osteocalcin and type I procollagen C-peptide increased during rhIGF-1 therapy (P < 0.05). Twenty-four hour urinary calcium, hydroxyproline, and pyridinoline cross-links were also higher after treatment than they were before treatment (P < 0.05). During 6 months of treatment, the bone mineral density of the L2 to L4 vertebrae increased 3%; this value exceeded the coefficient of variation of this measurement. Bone density at the femoral neck and radial shaft changed by less than the coefficient of variation of these measurements. No significant changes in serum glucose values or other adverse effects of treatment were noted.

Conclusions: Treatment with rhIGF-1 increased both bone formation and resorption in a patient with the Werner syndrome, a low baseline serum IGF-1 level, and established osteoporosis. Because lumbar bone mass increased without evidence of bone loss in the appendicular skeleton, a net increase in bone formation (formation greater than resorption) may have been responsible.

Author and Article Information

From the University of Texas Southwestern Medical Center, Dallas, Texas.
Requests for Reprints: Craig D. Rubin, MD, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-8889.
Acknowledgments: The authors thank Dr. Neil Gesundheit and Genentech for providing the rhIGF-1; Beverley Adams-Huet for data management and analysis; and John Poindexter for technical support.
Grant Support: By National Institutes of Health grants M01-RR00633 and R01-AR16061. Dr. Rubin is the recipient of Academic Award K08-AG00481 from the National Institute on Aging.