Garnero Patrick, Bauer Doug C, Mareau Emmanuel, Bilezikian John P, Greenspan Susan L, Rosen Clifford, Black Dennis
INSERM Research Unit 664, Lyon, France
J Bone Miner Res. 2008 Sep;23(9):1442-8. doi: 10.1359/jbmr.080413.
Fracture efficacy of PTH and alendronate (ALN) is only partly explained by changes in BMD, and bone collagen properties have been suggested to play a role. We analyzed the effects of PTH(1-84) and ALN on urinary alphaalpha/betabeta CTX ratio, a marker of type I collagen isomerization and maturation in postmenopausal women with osteoporosis. In the first year of the previously published PaTH study, postmenopausal women with osteoporosis were assigned to PTH(1-84) (100 microg/d; n = 119), ALN (10 mg/d; n = 60), or PTH and ALN together (n = 59). We analyzed patients on ALN alone (n = 60) and a similar number of patients assigned to PTH alone (n = 63). During the second year, women on PTH in the first year were reallocated to placebo (n = 31) or ALN (n = 32) and women with ALN continued on ALN. During the first year, there was no significant change in alphaalpha/betabeta CTX ratio with PTH or ALN. At 24 mo, there was a marked increase of the alphaalpha/betabeta CTX ratio in women who had received PTH during the first year, followed by a second year of placebo (median: +45.5, p < 0.001) or ALN (+55.2%, p < 0.001). Conversely, the alphaalpha/betabeta CTX ratio only slightly increased (+16%, p < 0.05) after 2 yr of continued ALN. In conclusion, treatment with PTH(1-84) for 1 yr followed by 1 yr of placebo or ALN may be associated with decreased type I collagen isomerization. The influence of these biochemical changes of type I collagen on bone fracture resistance remains to be studied.
甲状旁腺激素(PTH)和阿仑膦酸盐(ALN)的骨折疗效仅部分由骨密度变化来解释,有研究表明骨胶原特性也发挥了作用。我们分析了PTH(1-84)和ALN对绝经后骨质疏松症女性尿中αα/ββCTX比值的影响,该比值是I型胶原异构化和成熟的标志物。在之前发表的PaTH研究的第一年,将绝经后骨质疏松症女性分为PTH(1-84)组(100微克/天;n = 119)、ALN组(10毫克/天;n = 60)或PTH与ALN联合组(n = 59)。我们分析了仅接受ALN治疗的患者(n = 60)以及数量相近的仅接受PTH治疗的患者(n = 63)。在第二年,第一年接受PTH治疗的女性被重新分配至安慰剂组(n = 31)或ALN组(n = 32),而接受ALN治疗的女性继续使用ALN。在第一年,PTH或ALN治疗后αα/ββCTX比值无显著变化。在24个月时,第一年接受PTH治疗、第二年接受安慰剂治疗的女性,其αα/ββCTX比值显著升高(中位数:+45.5,p < 0.001);接受ALN治疗的女性,αα/ββCTX比值也显著升高(+55.2%,p < 0.001)。相反,持续使用ALN 2年后,αα/ββCTX比值仅略有升高(+16%,p < 0.05)。总之,PTH(1-84)治疗1年,随后1年使用安慰剂或ALN,可能与I型胶原异构化减少有关。I型胶原这些生化变化对骨折抵抗力的影响仍有待研究。