Osteoporosis (OP) is the most common multifactorial metabolic bone disorder worldwide. It remains unclear whether bisphosphonate (BP) pre-treatment affects the anabolic bone metabolism in OP patients treated with teriparatide (TPTD), a recombinant form of parathyroid hormone 1-34. This study is the first to evaluate the clinical outcomes of daily TPTD administration in Japanese OP patients and aimed to clarify how BP pre-treatment influences the efficacy of TPTD. We enrolled 112 patients diagnosed as primary OP who received TPTD. Subjects were classified as OP treatment-naïve patients (TPTD alone group) or patients previously treated with BP (BP pre-treated group). We measured serum bone-specific alkaline phosphatase (BAP) as a bone formation marker, urinary cross-linked N-terminal telopeptide of type I collagen (NTX) as a bone resorption marker, and bone mineral density (BMD) of lumbar vertebrae (L-BMD) and bilateral total hips (H-BMD). In both groups, BAP and NTX increased until 6 months and then decreased thereafter. The percent changes of both markers in BP pre-treated group were more increased than those in TPTD alone group. L-BMD increased significantly in both groups. The percent increase of L-BMD in the TPTD alone group was significantly higher than that in the BP pre-treated group. H-BMD rose significantly in the TPTD alone group, but not in BP pre-treated group. BP pre-treatment appears to diminish the degree of the TPTD-mediated increase in BMD. Thus, it is preferable to administer TPTD ahead of BP treatment in patients with severe OP.