Growth hormone injections improve bone quality in a mouse model of osteogenesis imperfecta.

UNLABELLED: Systemic growth hormone injections increased spine and femur length in a mouse model of OI. Femur BMC, cross-sectional area, and BMD were increased. Smaller gains were produced in vertebral BMC and cross-sectional area. Biomechanical testing showed improvements to structural and material properties in the femur midshaft, supporting expanded testing of growth hormone therapy in children with OI. INTRODUCTION: Osteoblasts in heterozygous Cola2oim mutant mice produce one-half the normal amounts of the alpha2 strand of type I procollagen. The mice experience a mild osteogenesis imperfecta (OI) phenotype, with femurs and vertebrae that require less force than normal to break in a biomechanical test. MATERIALS AND METHODS: Subcutaneous injections of recombinant human growth hormone (rhGH) or saline were given 6 days per week to oim/+ mice between 3 and 12 weeks of age, in a protocol designed to simulate a trial on OI children. RESULTS: rhGH injections promoted significant weight gain and skeletal growth compared with saline-treated control animals. Femur and spine lengths were increased significantly. Significant increases at the femur midshaft in cortical BMD (2.2%), BMC (15.5%), and cross-sectional area (13%) were produced by rhGH treatment. Increases in the same cortical bone parameters were measured in the metaphyseal region of the femur and in tail vertebrae, but lumbar vertebrae showed significant increases in BMC (9.6%) and cross-sectional area (10.1%) of trabecular bone. Three-point bending testing documented functional improvements to the femur mid-shafts. GH treatment produced significant increases in bone stiffness (23.7%), maximum load (30.8%), the energy absorbed by the femurs to the point of maximum load (44.5%), and the energy to actual fracture (40.4%). The ultimate stress endured by the bone material was increased by 14.1%. CONCLUSIONS: Gains in bone length, cross-sectional area, BMD, BMC, structural biomechanical properties, and strength were achieved without directly addressing the genetic collagen defect in the mice. Results support expanded clinical testing of GH injections in children with OI.

Resveratrol inhibition of Propionibacterium acnes.

OBJECTIVES: To evaluate the effects of the anti-inflammatory hydroxystilbene, resveratrol, on Propionibacterium acnes growth. METHODS: Three different strains of P. acnes were tested against resveratrol at concentrations between 0 and 200 mg/L. Piceatannol was included as a second hydroxystilbene to compare with resveratrol, and erythromycin and benzoyl peroxide were used as positive controls. RESULTS: After 24 h of treatment with resveratrol, the average 50% inhibitory concentration (IC(50)) was 73 mg/L and the average 100% inhibitory concentration (IC(100)) was 187 mg/L for the three strains of P. acnes tested. The IC(50) and IC(100) of piceatannol were 123 and 234 mg/L, respectively. The highest concentration of resveratrol tested (200 mg/L) was bactericidal, whereas lower concentrations were bacteriostatic. CONCLUSIONS: Resveratrol, an anti-inflammatory hydroxystilbene, is capable of inhibiting P. acnes growth.

Effects of growth hormone transgene expression on vertebrae in a mouse model of osteogenesis imperfecta.

STUDY DESIGN: A human growth hormone transgene was bred into mice of the Cola2oim (oim) lineage. Caudal (tail) vertebrae from male and female mice at early skeletal maturity and at midlife were evaluated for physical and biomechanical properties. OBJECTIVE: To test whether constant low-level growth hormone expression within the marrow could improve structural or material properties of caudal vertebrae in oim mice. SUMMARY OF BACKGROUND DATA: A spontaneous genetic defect in a type I procollagen gene created the oim mouse model for osteogenesis imperfecta. Bones of heterozygous oim mice are biomechanically inferior to wild-type controls. Bone marrow expression of human growth hormone was demonstrated previously to enhance bone deposition and structural biomechanical properties in caudal vertebrae of transgenic mice. METHODS: Compression tests were performed individually on three caudal vertebrae (Ca4, 5, and 6) from each mouse to determine their structural biomechanical properties. Volumetric and mineral content measurements were also made. In a subset of vertebrae, the ashing measurements were confirmed and extended by peripheral quantitative tomographic scanning, which also allowed calculation of the failure stress. RESULTS: Heterozygous oim mouse vertebrae had structural and material properties inferior to the wild-type controls. Growth hormone transgene expression increased the size and mineral content of the vertebrae from mutant mice, and increased biomechanical structural values for maximum load and energy to failure. Failure stress was not improved. CONCLUSIONS: Growth hormone stimulation of size and bone mineral content of osteogenesis imperfecta mutant mouse caudal vertebrae contributed to their improved performance in axial compression. There was no evidence for improved material properties, however.