RF30 | PSAT138 Romosozumab-aqqg in the Treatment of Osteoporosis in a Patient with Hypophosphatasia

BACKGROUND: Hypophosphatasia (HPP) is a rare inherited condition that causes osteomalacia and recurrent fractures. Therapeutic options for osteoporosis in patients with concomitant HPP are limited due to concerns for a greater likelihood of atypical femoral fractures (AFF) with anti-resorptive agents such as bisphosphonates and denosumab. We present a patient with HPP and OP who was treated with the anti-sclerostin antibody romosozumab-aqqg (Romo). CLINICAL CASE: An 81-year-old female was referred for management of OP. Fracture history included a hip fracture around age 40, and bilateral metatarsal fractures around age 65. Her initial DXA scan at age 57 showed osteoporosis at the lumbar spine (LS, T-score: -2.8) and femoral neck (FN, T-score -3.2). Sequential osteoporosis treatment over the subsequent 20 years included several years of oral bisphosphonates, hormone replacement therapy, teriparatide for one year followed by two years of alendronate, and one denosumab injection. Despite almost 20 years of pharmacologic osteoporosis treatment, her bone mineral density (BMD) worsened. HPP was suspected on the basis of low serum alkaline phosphatase (AP) levels ranging from 25-37 U/L (ref: 35-104 U/L). The diagnosis was substantiated by an elevated plasma vitamin B6 level of 305 mcg/L (ref: 5-50 mcg/L) and confirmed by genetic testing showing a diagnostic missense mutation c.571G>A in exon 6 in the ALPL gene. After diagnosing HPP, her osteoporosis was treated with an additional year of teriparatide followed by raloxifene, which she tolerated poorly. Following two years of expectant management, during which time her BMD worsened despite calcium and vitamin D supplementation to T-scores of –4.4 at the LS, she was started on Romo. After 11 monthly injections, a follow up DXA scan showed improvements of 21%, and 10% at the LS and total hip, respectively. These changes were substantially greater than what she experienced with her first year of teriparatide therapy (+4% and +8%, respectively). Blood AP remained low on Romo (37 IU/L and 29 IU/L at 9 and 12 months post-Romo initiation). She tolerated Romo and well and experienced no fractures during treatment. DISCUSSION: Management of osteoporosis in patients with HPP is challenging, as bisphosphonates and denosumab are generally avoided due to concern for an increased risk of AFF. Case reports of patients with HPP have suggested good BMD response to teriparatide. To our knowledge, this is the first report of a patient with HPP and osteoporosis treated with Romo. In our patient, Romo did not significantly impact serum AP, but improved BMD significantly more than in response to teriparatide. In conclusion, Romo is a potential treatment option for OP in patients with HPP for whom limited alternatives exist. Optimal osteoporosis treatment following a 1-year course of Romo remains to be determined. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:05 p.m. - 1:11 p.m.