SUN-741 Bone Mineral Density in Adults With Hypophosphatasia With or Without History of Fractures

Abstract Disclosure: L. Seefried: Alexion, AstraZeneca Rare Disease. P.S. Kishnani: Alexion, AstraZeneca Rare Disease. K.M. Dahir: Alexion, AstraZeneca Rare Disease. C. Rockman-Greenberg: Alexion, AstraZeneca Rare Disease. K. Ozono: Alexion, AstraZeneca Rare Disease. G.A. Martos Moreno: Alexion, AstraZeneca Rare Disease. W. Högler: Alexion, AstraZeneca Rare Disease. A. Linglart: Alexion, AstraZeneca Rare Disease. A. Petryk: Alexion, AstraZeneca Rare Disease. S. Fang: Alexion, AstraZeneca Rare Disease. P.R. Ebeling: Alexion, AstraZeneca Rare Disease. Rationale: To describe prevalence of patients with bone mineral density (BMD) T-scores ≤−2.5 by age in adults with hypophosphatasia (HPP) with and without history of fracture (HoF). Methods: Fractures occurring before asfotase alfa treatment (or at any time in untreated patients) were analyzed in younger (aged 18-≤50 y) and older (aged >50 y) adults from the Global HPP Registry (data cut: June 2023). Dual X-ray absorptiometry (DXA) results within 12 months of fracture (or most recent DXA for patients without HoF) were deemed evaluable. Sites analyzed included lumbar spine, hip neck, and total hip. T-scores <−2.5 were interpreted as osteoporosis. BMD T-scores (median [min, max; n), difference in medians (DM), and 95% confidence intervals (CIs) are presented. Results: The study included 278 younger adults (106 with HoF) and 249 older adults (142 with HoF). In younger adults, 17 with HoF and 86 without HoF had an evaluable DXA. Median T-scores were within a normal range in younger adults, although they were lower for those with HoF vs those without HoF at the lumbar spine (−1.2 [−2.8, 1.2; n=13] vs 0 [−1.9, 2.3; n=75]; DM: −1.1; CI: −1.9, −0.4), hip neck (−1.4 [−2.6, 0.6; n=12] vs −0.4 [−2.4, 1.4; n=61]; DM: −0.8; CI: −1.4, −0.1), and total hip (−1.3 [−2.5, 0.4; n=11] vs −0.3 [−2.2, 1.7; n=53]; DM: −0.9; CI: −1.5, −0.3). Few younger adults with HoF had T-scores ≤−2.5 (lumbar spine: 1/13 [8%]; hip neck: 2/12 [17%]; total hip: 1/11 [9%]). No younger adults without HoF had T-scores ≤−2.5. Median age at DXA was 33.9 y in those with HoF and 37.9 y in those without HoF. In older adults, 16 with HoF and 56 without HoF had an evaluable DXA. Median T-scores were within a normal range in older adults and were similar between those with HoF vs those without HoF at the lumbar spine (−0.8 [−4.1, 3.8; n=16] vs −0.8 [−3.8, 5.4; n=51]; DM: −0.3; CI: −1.4, 0.9), hip neck (−1.5 [−3.7, −0.3; n=16] vs −1.4 [−3.5, 0.7; n=44]; DM: 0; CI: −0.6, 0.7), and total hip (−1.6 [−2.9, 0.5; n=13] vs −1.1 [−3.4, 1.7; n=38]; DM: −0.8; CI:−1.5, 0.1). The percent of patients with T-scores ≤−2.5 was similar between those with vs without HoF (lumbar spine: 4/16 [25%] vs 11/51 [22%]; hip neck: 3/16 [19%] vs 13/44 [30%]; total hip: 3/13 [23%] vs 3/38 [8%]). Median age at DXA was similar in those with vs without HoF (60.6 y vs 60.8 y). Metatarsal/femoral fractures characteristic of HPP were present in 10/17 (59%) younger adults and 9/16 (56%) older adults; fractures characteristic of osteoporosis/low BMD (eg, vertebra, hip, wrist, humerus) were present in 5/17 (29%) younger adults and 7/16 (44%) older adults. Conclusions: Median BMD T-scores were within a normal range in adults regardless of fracture history. Some patients may have concomitant osteoporosis in addition to the underlying HPP-related osteomalacia. Further analysis to distinguish fractures due to osteoporosis vs compromised mineralization is warranted. Presentation: Sunday, July 13, 2025