Effects of PTH and Alendronate on Type I Collagen Isomerization in Postmenopausal Women With Osteoporosis: The PaTH Study

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 αα/ββ 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 μg/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 αα/ββ CTX ratio with PTH or ALN. At 24 mo, there was a marked increase of the αα/ββ 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 αα/ββ 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.