Positive Effects Of Parathyroid Hormonel-34on Microdamage Repair, Bone Turnover And BMD Of Ovariectomized Rats

Objective:To discuss the effect of parathyroid hormone (PTH1-34) on the bone microdamage repair, bone remolding, bone turnover and bone mineral density (BMD) of ovariectomized rats after fatigue loading, and explore the possible mechanism.Method:46female SD rats were randomly divided into PTH treated group and blank control group, after random drawing6rats as baseline group. Rats were successfully ovariectomized and subjected to fatigue load on the right ulna, then injected with PTH1-34in the therapeutic dose of40μg/kg or isometric vehicle subcutaneous. They were double-tagged in vivo and then sacrificed after treated for2or3weeks. BMD and BMC at lumbar spine (L1-L6), right femur, right tibia and bilateral ulnae were measured by DXA, right ulna were stained in basic fuchsin and embedding appropriately. Subsequently, thick sections were cut sequentially, and then microdamage parameters were observed using microscope. Bilateral radiuses were detected for the osteogenic expression of RUNX2and OPG, osteoclast expression of NFATc1using immunohistochemical and Western Blot method. Serum concentration of N-terminal propeptide of type I procollagen(PINP), Tartrate Resistant Acid Phosphatase form5b (TRACP5b) and osteocalcin(OC) were measured using ELISA method. The third lumbar vertebrae were ashed and weighted for the mineral content.Result:1. Microcrack density (Cr.Dn) and microcrack surface density (Cr.S.Dn) of the rats in PTH1-34treated for3weeks group decreased compare to control group, while there were no statistic difference in mean microcrack length (Cr.Le) and cortical thickness (Cr.Th). However, the microdamage parameters were not significant changed after2weeks treatment of PTH1-34.2. Two weeks of intermittent mechanical loading and subsequent PTH1-34treatment synergistically lead to increased BMC (bone mineral content) and BMD (bone mineral density) in right ulna, while there is no statistical difference in left ulna between PTH treatment group and control group.3. Protein expression of RUNX2and NFATc1increased in the loaded right radius of PTH1-34treated group compare to left radius. While the OPG expression of the right radius down-regulated.4. The serum concentration of PINP and osteocalcin(OC) were elevated in the PTH1-34treated for2weeks group compare to control group(P<0.01). The serum concentration of PINP increased in the PTH treated for3weeks group (P<0.01), while TRAP-5b were not altered compare to control group.5. As for the unloaded bone, PTH1-34treatment elevated both BMC and BMD in lumbar vertebras, femur and tibia(P<0.01). PTH1-34also increased bone mineral content of the lumbar vertebras, while the percentage of mineral content in lumbar vertebrae was not statistical altered.Conclusion:1. PTH1-34can accelerate the repair of microdamage, the possible mechanism was the elevated targeted bone remodeling repair process.2. Loading and PTH1-34synergistically increased bone density of cortical bone, the possible mechanism related to the elevated local osteogenic and osteoclast differentiation.3. PTH1-34increase BMD and BMC of bone, but cannot elevate percentage of mineral content of lumbar vertebra.