A Case of a Pre-Adolescent Female With a Triad of Bone Diseases

Demographics: 12 year 8 month old Caucasian female. Clinical Presentation: CM presented to the endocrinology clinic at age 10 years 3 months with lumbar and lower thoracic vertebral compression fractures. She was referred from the orthopedic clinic for endocrine evaluation of back pain and osteoporosis. She had spine x-rays and MRI which indicated severe osteoporosis, and significant loss of vertebral body height in the thoracolumbar region. Past History: She was the product of fraternal twin gestation, with birth weight of 5 lb, 11 oz. Previous fractures of the clavicle and finger have been reported. She has central obesity with BMI 26.6 kg/m (N97%). She drinks little milk, does not take vitamins, and participates in age-appropriate activities. Twin is unaffected. Evaluation: Height is 135 cm (10-25%ile), and weight is 48.4 kg (75-90%ile). Physical exam reveals a buffalo hump on the upper back, without abdominal striae. Laboratory assessments include: IGF-1 71 (117–771 ng/mL), 25-hydroxy vitamin D 20 ng/mL, alkaline phosphatase 216 (80–240 units/L), thyroid function studies normal, parathyroid hormone normal, morning cortisol 19.0 (2.9-19.4 μg/mL), urinary free cortisol 10.3 (1.0-45.0 μg/ 24 hr), growth hormone stimulation test using arginine and insulin with growth hormone maximum 0.8 ng/mL, and genetic testing for collagen mutation revealed a COL1A2 mutation consistent with osteogenesis imperfecta (OI). Radiologic assessments include: bone age 11 years at 10 years 3 months, and pituitary MRI normal. DEXA scan revealed bone mineral density (BMD) significantly below the expected range for the patient age. Interventions: CM was started on vitamin D supplementation 2000 IU/day for vitamin D deficiency. She was begun on growth hormone therapy at a dose of 0.3 mg/kg per week for severe growth hormone deficiency. Two years post therapy reveals no back pain, decreased fracture rate, increase in height to the 50th percentile, normal IGF-1, significant improvement in BMD, and repair of compressed vertebrae. Discussion: Both growth hormone deficiency and OI can contribute to loss of bone integrity, resulting in osteopenia or osteoporosis. The combination of these two conditions has resulted in significant impact upon the bony structure. Replacement with growth hormone only has demonstrated significant improvement in her medical condition.