[Effects of teriparatide and alendronate on bone mineral density of osteoporotic rats].
OBJECTIVE
To investigate the effects of teriparatide (hPTH1-34, PTH) and alendronate (Alen) on bone turnover rate and bone mineral density (BMD) of ovariectomized (OVX) osteoporotic rats.


METHODS
70 female 6-month-old Wistar rats were randomly divided into 7 groups: (1) baseline group: killed immediately as baseline controls; (2) sham operation group: injected subcutaneously with normal saline (NS) as normal controls; (3) OVXb group: underwent ovarietomy (OVX) and killed 6 weeks after OVX as pre-therapeutic controls; (4) OVXe group: injected with NS subcutaneously and then sacrificed 14 weeks after OVX as controls by the end of treatment; (5) PTH group: PTH 40 microg.kg(-1).d(-1) was administered; (6) Alen group: Alen 100 microg.kg(-1).d(-1) was administered; (7) A + P group: PTH 40 microg.kg(-1).d(-1) and Alen 100microg.kg(-1).d(-1) were administered. In groups 4 approximately 7, different medicines were injected subcutaneously QD 5 times per week from the 6th week to the 14th week after OVX and then the rats were killed and their right femurs, lumbar vertebrae, and samples of blood and urine were collected. Absorptometry was used to measure the BMD of the right femur and lumbar vertebrae. The serum calcium, phosphate, creatinine, alanine transaminase, and alkaline phosphatase (ALP) activity were measured by automatic biochemical analysis. The bone resorption marker urine deoxypyridinoline/creatinine (UDpd/Cr) level was measured by enzyme-linked immuosorbent assay.


RESULTS
Six weeks after OVX the ALP and UDpd/Cr levels in the OVXb group were 101 U/L +/- 59 U/L and (118 +/- 32) x 10(-6) respectively, both significantly higher than those of the baseline group (58 U/L +/- 10 U/L and (48 +/- 34) x 10(-6) respectively, both P < 0.01) and the BMD results of the OVXb group were all significantly lower than those in the baseline group (all P < 0.01), which indicated that an OVX osteoporotic rat model was established successfully. The ALP and UDpd/Cr levels of the Alen group were 61 U/L +/- 28 U/L and (17 +/- 39) x 10(-6), significantly lower than those of the PTH group 120 U/L +/- 36 U/L and (111 +/- 26) x 10(-6) respectively, both P < 0.01) and the UDpd/Cr levels of the A + P group were between those of the Alen group and those of the PTH group. The BMD levels of the femur and lumbar vertebrae of the PTH, Alen, and A + P groups were all significantly higher than those of the control groups (all P < 0.01), and were similar to or higher than those of the sham operation group without significant differences between the PTH and Alen groups. The BMD level of the lumber vertebrae of the A + P group were significantly higher than those in the PTH group (all P < 0.05), and the femoral BMD results of the A + P group were significantly higher than those in the PTH and Alen groups (all P < 0.01).


CONCLUSIONS
PTH and Alen are all effective on osteoporosis. In particular, the combination of PTH and Alen is more effective on increasing the BMD level.
Li
Mei
M
Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Jiao
Jie
J
Meng
Xu-wu
XW
Xing
Xiao-ping
XP
Xia
Wei-bo
WB
Zhou
Xue-ying
XY
Liu
Huai-cheng
HC
Jiang
Yan
Y
Wang
Ou
O
Hu
Ying-ying
YY
Zhan
Zhi-Wei
ZW
D019386:Alendronate / Q000627:therapeutic use*; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D010024:Osteoporosis / Q000188:drug therapy* / Q000209:etiology; D010052:Ovariectomy; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D019379:Teriparatide / Q000627:therapeutic use*
D019379:Teriparatide; D019386:Alendronate