Introduction: Hypophosphatasia (HPP) is a rare genetic disorder characterized by low serum alkaline phosphatase (ALP) and defective bone mineralization predisposing to poorly healing pseudofractures and fractures. Experience with teriparatide in HPP is limited. Methods: A 53-yr-old woman was diagnosed with HPP on the basis of repeatedly low serum ALP (6-8 IU/liter; normal, 30-120 IU/liter), high urine phosphoethanolamine (PEA) and serum pyridoxal 5′-phosphate (PLP) concentrations, and pseudofractures on the lateral aspect of both proximal femurs. Teriparatide (20 μg/d sc) was initiated 4 months after surgery for a painful nonhealing left femoral fracture sustained after minimal trauma. Results: The patient carried two missense mutations at exons 6 and 11 (Ala176Thr and Val423Ala) and one polymorphism at exon 12 (Val522Ala) of the tissue nonspecific ALP gene (TNSALP). Pain resolved and mobility improved with teriparatide treatment. Serum ALP doubled, and both urine PEA and serum PLP decreased. Markers of bone remodeling increased markedly. Comparison of bone biopsy before and 5 months after teriparatide revealed increased amounts of osteoid and osteoblast numbers. After 8 months, there was complete healing of the pseudofracture of the right femur, and bony callus was apparent on the left. Despite good compliance, serum ALP and PLP and urine PEA returned to baseline with between 8 and 13 months of treatment. Conclusion: This is the first bone biopsy report of teriparatide response in adult HPP. In contrast to the two previously reported cases, biochemical response to teriparatide was unsustained, suggesting that response may be variable depending on the TNSALP gene mutation.