Fig. 1

Characteristics of OI patients with homozygous WNT1 mutations. a Overview of four OI-XV patients, including sex, age, WNT1 mutation, presence of mental retardation/neurological phenotype (MR/NP), and number of vertebral and peripheral fractures (Vert. Fx, Per. Fx). b Cranial magnetic resonance imaging (cMRI, sagittal and axial view) showing hydrocephalus and brain atrophy in patient #2. c Dual X-ray energy absorptiometry (DXA) Z-scores in the two patients without brain effects at baseline and after 1 year (case #3) or 3 years (case #4) of neridronate treatment. d Radiographs of patient #3 at the age of 5 years receiving neridronate treatment for one year showing a left diaphyseal femur fracture (arrow) before (left) and after (middle) surgical treatment via telescopic nail. Note the new right diaphyseal femur fracture (arrow). Spine radiography of the same patient revealed multiple vertebral fractures indicated by asterisks (right). e Timeline of fractures that occurred in patient #3. The orange line indicates the period of neridronate treatment. f Histological images of a proximal femur biopsy (cortical bone) from case #3 indicating an absence of osteomalacia (left, Trichrome-Goldner staining) and several multinucleated osteoclasts (right, toluidine blue staining). g Histomorphometric quantification of cortical porosity (Ct. Po), osteoblast surface per void surface (Ob.S./Vd.S), osteoclast surface per void surface (Oc.S./Vd.S), osteoid thickness (O.Th.), osteoid surface (OS/Vd.S) and osteoid volume (OV/BV) measured in the cortical region of a proximal femur biopsy from case #3 in comparison to a location-, age- and sex-matched control biopsy. h Quantitative backscattered electron imaging (qBEI) comparing the cortical region of the bone biopsy from Case #3 to a control biopsy. Gray levels indicate the mineral content. i Bone mineral density distribution (BMDD) histograms identify a slight shift toward lower mineralization in the patient biopsy (case #3)