OBJECTIVES: Osteoporosis is a disease with accelerated bone loss associated with an increased risk of fractures. Histomorphometry of bone biopsy specimens from postmenopausal women with osteoporosis measures bone remodeling activities which include both bone formation and resorption. This study compared the effects of two osteoporosis treatments (20 μg/day teriparatide vs. 10 mg/day alendronate) on bone remodeling using the principal components analysis (PCA) of bone histomorphometry parameters. METHODS: Postmenopausal women with osteoporosis treated with either teriparatide or alendronate and completed iliac crest bone biopsy at either the sixth or eighteenth month in the randomized, double-blind Forteo Alendronate Comparator Trial were included in the analysis (teriparatide: N=12; alendronate: N=9). Eighteen histomorphometric parameters were grouped into either the formation (13) or resorption (5) category. Within each category, the first principal component was estimated through the PCA and defined as the principal formation component (PFC) and principal resorption component (PRC). The summation of PFC and PRC was calculated to represent the overall level of bone turnover. The difference between PFC and PRC was computed to determine the imbalance between formation and resorption. RESULTS: The PFC accounted for 61.8% of total variance in the 13 formation parameters, and the PRC accounted for 70.4% of total variance in the 5 resorption parameters. The PFC was significantly higher in the teriparatide group than in the alendronate group (0.68 vs. -0.95, p<0.0001), while the PRC was significantly lower in the alendronate group (-0.47 vs. 0.32, p<0.05). The difference between the PFC and PRC was positive in the teriparatide group and negative in the alendronate group. CONCLUSIONS: In postmenopausal women with osteoporosis, teriparatide treatment stimulates both bone formation and resorption, and formation dominates resorption. Treatment with alendronate suppresses both bone formation and resorption, and resorption dominates formation.