Effects of hypophysectomy and recombinant human growth hormone on material and geometric properties and the pre- and post-yield behavior of femurs in young rats.
To study the musculoskeletal effects of hypophysectomy (Hx) and a partial replacement treatment with recombinant human growth hormone (rhGH) in rats, we determined the stiffness (elastic modulus, E) and volumetric BMD (vBMD) of cortical bone; the periosteal and endosteal perimeters, area and bending moment of inertia (xCSMI) of the cross sections, and the structural stiffness and pre- and post-yield strength of the femur diaphyses by pQCT and mechanical tests, and the gastrocnemius weight of rats that were either intact (n = 9) or Hx at 15 days of age (20). The latter were otherwise untreated (Hx controls, 4) or given 0.4 (8) or 2.0 (8) IU kg(-1) day(-1), s.c., of rhGH for 45 days starting 15 days after surgery. Hx delayed musculoskeletal development (gastrocnemius weight, bone geometric properties), thus affecting the diaphyseal stiffness and strength. It also reduced the cortical vBMD through an undefined mechanism, and increased the elastic modulus of cortical bone. The Hx also affected the correlation between bone geometric and material properties (xCSMI vs. E), suggesting an antianabolic interaction with the biomechanical control of bone modeling in response to strains caused by mechanical usage. As a result, Hx reduced the stiffness, post-yield, and ultimate strength of the diaphyses. These effects should reflect changes in bone tissue microstructure, perhaps associated with crack generation and progress, but unrelated to bone mineral mass. They are compatible with the induction of a delay in collagen turnover with associated increases in fibers' diameter and crystals' size that may have resulted from the suppression of some other hormones, such as thyroid, prolactin, or other hormones regulated by ACTH. The above doses of rhGH significantly but incompletely prevented the negative Hx effects on bone and muscle development (bone geometric properties, muscle mass). However, rhGH treatment failed to prevent the demineralizing and stiffening effect of Hx on bone tissue and the unusual effects on the post-yield strength (less clearly related to muscle development than the former). Consequently, rhGH treatment tended to preserve the natural relationship between muscle function and bone geometry but not bone strength. The effects of larger rhGH doses and the interaction of other hormones with the described effects remain to be investigated. Nevertheless, these findings would deserve special attention because they challenge the prevailing view that in endocrine-metabolic bone-weakening diseases the bone matrix always has a normal composition.
Feldman
Sara
S
Centro de Estudios de Metabolismo Fosfocálcico (CEMFoC), Universidad Nacional de Rosario, Rosario, Argentina
Cointry
Gustavo R
GR
Leite Duarte
María E
ME
Sarrió
Leandro
L
Ferretti
José L
JL
Capozza
Ricardo F
RF
D000375:Aging / Q000502:physiology*; D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000187:drug effects* / Q000254:growth & development; D019382:Human Growth Hormone / Q000235:genetics / Q000494:pharmacology*; D007016:Hypophysectomy; D009132:Muscles / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D019382:Human Growth Hormone