title: Fractures on bisphosphonates in osteoporosis pseudoglioma syndrome (OPPG): pQCT shows poor bone density and structure.
abstract: Osteoporosis pseudoglioma syndrome (OPPG) is a rare autosomal recessive disorder of childhood osteoporosis and blindness due to inactivating mutations in LDL receptor-like protein 5 (LRP5). We and others have reported improvement in areal bone mineral density (aBMD) by DXA in OPPG on short term bisphosphonates. Long-term data on bisphosphonate use in OPPG and measures of volumetric BMD (vBMD) and cortical structure are not available. In addition, no long-term DXA data on untreated OPPG is available. The aims of this study were to: (1) record low trauma fractures and longitudinal aBMD by DXA in 5 OPPG patients on chronic bisphosphonate treatment, and in 4 OPPG patients never treated (2) to perform tibia peripheral quantitative CT (pQCT) to evaluate volumetric bone mineral density (vBMD), cortical structure and calf muscle area in 6 OPPG patients and 14 unaffected first degree family members. pQCT results were converted to sex-specific Z-scores for age and adjusted for tibia length based on data in >700 reference participants. We observed 4 fractures (3 femoral shafts) in 3 OPPG patients while on bisphosphonates, after each achieved significant improvement in aBMD. OPPG participants had significantly lower mean trabecular vBMD (-1.51 vs. 0.17, p = 0.002), cortical area (-2.36 vs. 0.37; p < 0.001) and periosteal circumference (-1.86 vs. -0.31, p = 0.001) Z-scores, compared with unaffected participants and had a trend toward lower muscle area Z-score (-0.69 vs. 0.47, p = 0.12). These data demonstrate substantial bone fragility despite improvements in aBMD. The pQCT data provide insight into the fragility with substantial deficits in trabecular vBMD and cortical dimensions, consistent with OPPG effects of bone formation. Treatment that improves bone quality is needed to reduce fractures in OPPG.
authors.affiliation: University of Maryland School of Medicine, Division of Endocrinology, Diabetes & Nutrition, Baltimore, MD, USA. Electronic address: estreete@medicine.umaryland.edu.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Streeten
authors.affiliation: University of Maryland School of Medicine, Division of Endocrinology, Diabetes & Nutrition, Baltimore, MD, USA.
authors.forename: Sheila
authors.initials: S
authors.lastname: Ramirez
authors.affiliation: University of Maryland School of Medicine, Division of Endocrinology, Diabetes & Nutrition, Baltimore, MD, USA.
authors.forename: Myrto
authors.initials: M
authors.lastname: Eliades
authors.affiliation: University of Maryland School of Medicine, Division of Endocrinology, Diabetes & Nutrition, Baltimore, MD, USA.
authors.forename: Sarada
authors.initials: S
authors.lastname: Jaimungal
authors.affiliation: University of Maryland School of Medicine, Division of Endocrinology, Diabetes & Nutrition, Baltimore, MD, USA.
authors.forename: Sruti
authors.initials: S
authors.lastname: Chandrasekaran
authors.affiliation: University of Maryland School of Medicine, Division of Endocrinology, Diabetes & Nutrition, Baltimore, MD, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Kathleen
authors.affiliation: The Clinic for Special Children, Strasburg, PA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Holmes Morton
authors.affiliation: The Clinic for Special Children, Strasburg, PA, USA.
authors.forename: Erik G
authors.initials: EG
authors.lastname: Puffenberger
authors.affiliation: Stanford University School of Medicine, Departments of Pediatrics and Medicine (Nephrology), Stanford, CA, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Herskovitz
authors.affiliation: Stanford University School of Medicine, Departments of Pediatrics and Medicine (Nephrology), Stanford, CA, USA.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Leonard
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D000328:Adult; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010013:Osteogenesis Imperfecta / Q000150:complications / Q000188:drug therapy*; D014057:Tomography, X-Ray Computed / Q000379:methods*; D055815:Young Adult
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates
keywords: Atypical femur fracture; Bone mineral density; OPPG; Osteoporosis pseudoglioma syndrome; pQCT