Seforno: It refers to the destruction of the second Beis-Hamikdash.

Rashbam: It refers to the land remaining barren ? corresponding to the number of years (seventy) that Yisrael negated Sh?mitah and Yovel, as the Pasuk goes on to explain.

Rashi #1: It means 'because of' (as a punishment for) ¹ (which presumably, the Torah repeats for emphasis).

Rashi #2 (in the initial edition) and Rashbam: What the Torah is saying is that it is because Yisrael despised Hashem's judgments and because they loathed His statutes that the land became bereft of them.

Targum Onkelos and Targum Yonasan: It implies that 'curses instead of blessings ² will come upon you'.

Moshav Zekenim (in 25:17): It is due to an evil response to an Oni. "Ya'an" is an expression of answering, and u'v'Ya'an are the letters of be'Oni.

Ramban: It is referring to the period after Koresh initially granted Yisrael permission to return to Eretz Yisrael and ordered the rebuilding of the Beis-Hamikdash, when the order was withdrawn, and the land continued to be bereft of Yisrael and the land continued to be appeased for the broken Shemitos for another nineteen years, until the second Beis-Hamikdash was built and they sanctified Yerushalayim with two Todos. ¹ That was when the Kedushah returned to the land and they once again kept the Shemitah. ²

Moshav Zekenim: The exile and afflictions are a better Kaparah for Yisrael than Korbanos. Wheres in connection with the Korbanos, the Torah writes "Venirtzeh lo Lechaper alav" (on the one sin), here it writes "ve'Heim Yirtzu es Avonam" (all their sins). ³