We previously demonstrated that an isocaloric low protein diet attenuates the bone anabolic response to GH. Whether such a dietary manipulation could affect the bone anabolic effects of PTH was assessed. We studied 6-month-old female rats pair fed with isocaloric diets with a low protein (2.5% casein, LP) or normal protein content (15% casein, NP) for 2 weeks. Then, the animals were treated with 5 or 40 μg/kg recombinant human amino-terminal fragment PTH(134) (PTH-5 and PTH-40), or with vehicle for 4 weeks. Before starting PTH treatment, the 2-week LP diet was associated with reduced plasma IGF1, but no change in bone strength nor microstructure. After 4 weeks of PTH, proximal tibia trabecular BMD, microarchitecture and compressive bone strength were increased in a dose dependent manner in NP. These changes were attenuated in rats fed the LP diet. In the cortical compartment, PTH was anabolic in NP but not in LP group. Bone cellular mechanisms underlying the attenuated bone anabolic response to PTH under LP were analyzed by histomorphometry. At trabecular level, osteoid surfaces were similarly dose-dependently increased by PTH treatment compared to vehicle treated and diet matched groups, in both in NP and LP, surprisingly osteoclastic surfaces were lower in PTH-treated NP. Trabecular bone formation rate was increased in PTH treated NP group (PTH-5:+271 and PTH-40:+443%), with a lower response in LP (PTH-5+171 and +343%). At the cortical level, periosteal and endosteal bone formation rate were increased by PTH-40 in both NP and LP, with a 30% greater periosteal formation in NP compared to LP.
In conclusion, protein malnutrition attenuates anabolic PTH response through lower bone formation cellular activities.
17 May 2014 - 20 May 2014