Samnegård E, Iwaniec U T, Cullen D M, Kimmel D B, Recker R R
Osteoporosis Research Center, Creighton University, Omaha, NE, USA.
Bone. 2001 Mar;28(3):251-60. doi: 10.1016/s8756-3282(00)00446-4.
The purpose of this cross-sectional study was to evaluate the effects of human parathyroid hormone(1-84) (hPTH) followed by maintenance treatment with 17beta-estradiol (E(2)), risedronate (Ris), or a reduced dose of hPTH (LowPTH) on cortical bone in the ovariectomized (ovx) rat. Eight groups of ovx and one group of intact female rats (3.5 months) were left untreated for 11 weeks. For the following 12 weeks, four groups received subcutaneous injections of hPTH (75 microg/kg per day on 3 days/week) and four groups received vehicle. Treatments were then changed to E(2) (10 microg/kg per day on 2 days/week), Ris (3 microg/kg per day on 3 days/week), LowPTH (25 microg/kg per day on 3 days/week), or vehicle. Bone tissue was collected at weeks -11 (baseline), 0 (ovx effect), 12 (hPTH effect), 24, 36, and 48 (maintenance effect). Bone mineral density (BMD) and bone mineral content (BMC) of the diaphyseal femur and total cross-sectional area (Tt.Ar), marrow area (Ma.Ar), cortical area (Ct.Ar), and periosteal and endocortical bone formation of the tibia were measured. Ovariectomy resulted in lower BMD (weeks 0-48), unaffected BMC, and greater Tt.Ar (weeks 12 and 36), Ma.Ar (week 48), and Ct.Ar (weeks 0 and 12) compared with intact rats. Endocortical and periosteal bone formation were greater in the ovx than in the intact rats up to 23 weeks postovariectomy. Treatment of ovx rats with hPTH for 12 weeks resulted in greater cortical BMD, BMC, and endocortical bone formation than in intact or ovx controls. In ovx rats pretreated with hPTH and then treated with Ris for 36 weeks, BMD and BMC were greater and Ma.Ar was smaller than in ovx controls. In ovx rats pretreated with hPTH and then treated with LowPTH, BMD, BMC, Ct.Ar, and endocortical bone formation were greater and Ma.Ar was smaller than in ovx controls. Treatment of hPTH-pretreated rats with E(2) for 36 weeks did not affect cortical BMD, BMC, and Ct.Ar, although periosteal bone formation was lower in the E(2) group compared with the ovx group. Thus, in ovariectomized rats, cortical bone gained by 12 weeks of hPTH treatment was maintained for up to 36 weeks by treatment with risedronate or low-dose hPTH, but not with 17beta-estradiol.
本横断面研究的目的是评估人甲状旁腺激素（1-84）（hPTH），随后用17β-雌二醇（E₂）、利塞膦酸盐（Ris）或低剂量hPTH（LowPTH）维持治疗对去卵巢（ovx）大鼠皮质骨的影响。八组去卵巢大鼠和一组完整雌性大鼠（3.5个月）未接受治疗11周。在接下来的12周里，四组接受皮下注射hPTH（每周3天，每天75μg/kg），四组接受赋形剂。然后治疗改为E₂（每周2天，每天10μg/kg）、Ris（每周3天，每天3μg/kg）、LowPTH（每周3天，每天25μg/kg）或赋形剂。在第-11周（基线）、0周（去卵巢效应）、12周（hPTH效应）、24周、36周和48周（维持效应）采集骨组织。测量股骨干的骨密度（BMD）和骨矿物质含量（BMC）以及胫骨的总横截面积（Tt.Ar）、骨髓面积（Ma.Ar）、皮质面积（Ct.Ar）以及骨膜和骨内膜的骨形成。与完整大鼠相比，去卵巢导致BMD降低（0-48周），BMC未受影响，Tt.Ar增大（12周和36周）、Ma.Ar增大（48周）以及Ct.Ar增大（0周和12周）。去卵巢后长达23周，去卵巢大鼠的骨内膜和骨膜骨形成比完整大鼠更明显。用hPTH治疗去卵巢大鼠12周导致皮质BMD、BMC和骨内膜骨形成比完整或去卵巢对照组更大。在先用hPTH预处理然后用Ris治疗36周的去卵巢大鼠中，BMD和BMC更大，Ma.Ar比去卵巢对照组更小。在先用hPTH预处理然后用LowPTH治疗的去卵巢大鼠中，BMD、BMC、Ct.Ar和骨内膜骨形成更大，Ma.Ar比去卵巢对照组更小。先用hPTH预处理的大鼠用E₂治疗36周不影响皮质BMD、BMC和Ct.Ar，尽管E₂组的骨膜骨形成比去卵巢组更低。因此，在去卵巢大鼠中，hPTH治疗1周获得的皮质骨通过利塞膦酸盐或低剂量hPTH治疗可维持长达36周，但用17β-雌二醇则不能。
