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


BACKGROUND
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.


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.
King
Donna
D
Department of Biochemistry and Molecular Pathology, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio 44272, USA. dk@neoucom.edu
Jarjoura
David
D
McEwen
Heather A
HA
Askew
Michael J
MJ
D000818:Animals; D001696:Biomechanical Phenomena; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects; D003094:Collagen / Q000235:genetics; D024042:Collagen Type I; D003720:Densitometry; D004195:Disease Models, Animal; D005269:Femur / Q000187:drug effects / Q000473:pathology; D050723:Fractures, Bone / Q000517:prevention & control; D013006:Growth Hormone / Q000627:therapeutic use*; D006579:Heterozygote; D006801:Humans; D008159:Lumbar Vertebrae / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010013:Osteogenesis Imperfecta / Q000188:drug therapy*; D010641:Phenotype; D013997:Time Factors
D024042:Collagen Type I; D013006:Growth Hormone; D003094:Collagen