Online Resource Table 3

‘Sink or swim’: an evaluation of the clinical characteristics of individuals with High Bone Mass. Osteoporosis International. Celia L Gregson et al. University of Bristol, Musculoskeletal Research Unit. [email protected]

Online Resource table 3

First sensitivity analysisa: The structural bone phenotype and buoyancy of High Bone Mass cases compared with unaffected family controls

Adj n HBM n(%) Control n(%) Unadj OR Unadj Adj OR p (535) (n=335) (n=200) (95%CI) p value (95%CI)e valuee The structural bone phenotype Mandible enlargement 417 100 (37.6) 24 (15.9) 3.19 (1.93, 5.27) <0.001 4.14 (2.33, 7.38) <0.001 Broad frame 342 115 (56.7) 52 (37.4) 2.19 (1.41, 3.40) 0.001 3.69 (2.16, 6.29) <0.001 Shoe size (UK sizing)a 451 7.1 (6.9, 7.4) 7.9 (7.6, 8.2) -0.8 (-1.2, -0.4) <0.001 0.4 (0.1, 0.6) 0.013 Misshapen or extra bone 525 59 (17.8) 26 (13.4) 1.44 (0.86, 2.42) 0.169 1.74 (0.97, 3.11) 0.061 reported Misshapen or extra bone 408 56 (21.5) 21 (14.2) 1.66 (0.96, 2.87) 0.07 2.07 (1.12, 3.81) 0.020 on examinationb

Torus palatinus & 435 88 (31.7) 49 (31.2) 1.02 (0.67, 1.56) 0.924 1.50 (0.92, 2.45) 0.105 torus mandibularis Dental overcrowding 464 87 (29.9) 60 (34.7) 0.80 (0.54, 1.20) 0.287 0.82 (0.52, 1.30) 0.399 Report of oral structural 526 27 (8.2) 10 (5.1) 1.67 (0.78, 3.60) 0.187 1.97 (0.85, 4.58) 0.113 abnormalityc

Webbing of toes 378 12 (5.1) 6 (4.2) 1.21 (0.45, 3.31) 0.704 1.54 (0.48, 4.93) 0.462 Hammer toes 481 42 (13.6) 9 (5.2) 2.85 (1.35, 6.04) 0.006 2.25 (0.99, 5.12) 0.054 Carpal tunnel syndromed 535 21 (6.3) 5 (2.5) 2.73 (0.99, 7.58) 0.053 2.1 (0.73, 6.04) 0.168 Abnormal spine 394 99 (39.8) 35 (24.1) 2.07 (1.31, 3.28) 0.002 1.67 (0.98, 2.85) 0.060 Spinal kyphosis 481 22 (7.1) 10 (5.8) 1.24 (0.57, 2.69) 0.582 0.71 (0.29, 1.73) 0.457 Spinal scoliosis 481 18 (5.8) 3 (1.7) 3.53 (1.01, 12.36) 0.048 3.52 (0.91, 13.64) 0.069 Categories of Buoyancy Floats 161 (48.5) 143 (72.6) 1.00 1.00 Struggles to float 24 (7.2) 16 (8.1) 1.36 (0.67, 2.77) 1.89 (0.86, 4.13) 497 <0.001 0.002 Sinks 108 (32.5)f 15 (7.6) 6.85 (3.70, 12.71) 6.87 (3.53, 13.38) Unable to swim 19 (5.7) 11 (5.6) 1.54 (0.68, 3.48) 1.15 (0.45, 2.94) OR: clustered Odds Ratio, CI: Confidence Interval a Exclusion of: 13 women with history of HRT implants who did not have affected first-degree relatives, 1 case who reported lithium treatment but who lacked an affected first-degree relative, 1 patient with myelofibrosis, 1 with acromegaly, 3 with possible X-linked hypophosphataemic rickets (based upon serum phosphate level of <0.70 mmol/l and bridging osteophytes of the lower thoracic and upper lumbar spine, of whom one also had evidence of new bone formation at the pelvis and upper femorae. Whilst radiological features were consistent with diffuse idiopathic skeletal hyperostosis (DISH), in combination with low phosphate these may represent the enthesopathy reported in X-linked hypophosphataemic rickets (27), although other clinical features such as short stature, a family history or a history of fragility fractures were absent), 1 with investigations for possible ankylosing spondylitis a Means and mean differences given for this continuous variable b Includes increased bone at sites of tendon & ligament insertion (tibial tuberosity, patella boarder, calcaneus at point of Achilles tendon, head of the fibula and clavicle, olecranon, ulna styloid, radial head, navicular bone, MCP, PIP), bony swelling within ribs / costo-cartilage junctions, focal increases in bone over the tibia and skull, global increases in skull size, prognatism, asymmetry of the mandible, chest wall, orbits and scapulae, including Sprengel’s and Madelung’s deformities, camptodactaly, abnormally shaped patellae and pelvis, congenitally short digits, metacarpals and absent bone in toes c Oral Structural abnormalities include: eruption of extra sets of teeth, failure of eruption of adult teeth, persistent milk teeth into adulthood, eruption of teeth through palate, convex palate, cleft palate, extra bone in mouth d Carpal tunnel syndrome reported or previously operated e Adjusted for age at recruitment, gender f 2 HBM cases reported sinking in the Dead Sea despite the sea’s high specific gravity