If oversuppression of bone turnover explained the association between bisphosphonate use and atypical subtrochanteric femur fractures (AFF), this could be reversed with anabolic treatment such as teriparatide. We conducted a prospective, open-label study in patients previously treated with bisphosphonates who sustained AFF, examining the response to 24-month treatment with teriparatide on bone mineral density (BMD), trabecular bone score (TBS), bone turnover markers (BTM), and fracture healing as well as quantitative histomorphometry. We studied 14 patients. Baseline BMD, BTM, and TBS varied widely. On initial bone biopsies, 12 of 14 patients showed tetracycline labels, but mineralizing surface/bone surface was below published normal values in all but 2. Lumbar spine BMD increased significantly at month 24 (6.1% ± 4.3%, p < 0.05 versus baseline), whereas total hip BMD and TBS did not change significantly. Changes in BTM occurred as reported previously for patients without AFF treated with teriparatide after prior bisphosphonate treatment. At month 24, fractures were healed in 6 patients, showed partial healing in 3, were unchanged in 2, and showed nonunion in 1. In a patient with two fractures, the fracture that occurred before teriparatide treatment was reported as healed, but the fracture that occurred while on treatment showed only partial healing. Bisphosphonate-treated patients who sustain AFF show heterogeneity of bone turnover. Treatment with teriparatide resulted in increases in BTM and lumbar spine BMD, as has been reported for patients without AFF. There was no significant effect of teriparatide on hip BMD, mineralizing surface to bone surface (MS/BS), or TBS and no consistent effect on fracture healing. In the context of a patient who has experienced an AFF after receiving bisphosphonate treatment, therapy with teriparatide for 24 months would be expected to increase BMD and BTM (and probably reduce the risk of fractures resulting from osteoporosis) but should not be relied on to aid in healing of the AFF. © 2017 American Society for Bone and Mineral Research.

Infants and children with hypophosphatasia (HPP) treated with asfotase alfa show improvement in bone mineralization and motor function, but it is unclear whether the medication can affect fracture healing in adult HPP patients. We present the course of fracture healing in two adults with HPP on enzyme replacement. Case 1 is a 41‐year‐old female with infantile‐onset HPP who was wheelchair‐bound due to a nonhealing tibial fragility fracture sustained 3 years before and also had nonhealing femoral pseudofracture sustained 17 years before starting asfotase alfa therapy in December 2015. One month after medication initiation, she underwent elective osteotomy of tibia and fibula with intramedullary nail fixation. After 3 months of enzyme replacement, she was full weight‐bearing and radiographs demonstrated callus formation at osteotomy sites, and at 11 months of therapy, radiographs showed union of the osteotomies. By 11 months of asfotase alfa therapy, there was near resolution of the femoral pseudofracture without interval surgery at this site. Case 2 is a 61‐year‐old male who showed nonunion of a fragility fracture of the right femur 8 years prior, intramedullary nail fixation 6 years prior, and stress fracture of the left femoral diaphysis sustained 1 year before starting asfotase alfa in October 2015. A trial of teriparatide was unsuccessful in healing of these fractures. On asfotase alfa, radiographs revealed interval healing of the left femur fracture after 12 months and complete healing of the right femur fracture and near resolution of the left femur fracture after 16 months of medical therapy. These two adult patients with HPP showed significant clinical and radiographic improvements in a total of four recalcitrant fractures on enzyme replacement therapy with asfotase alfa. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.