30, 4.04)i 0.892i Fracture after aged 45 541 40 (11.6) 17 (8.7) 1.38 (0.75, 2.54) 0.304 0.88 (0.43, 1.81)i 0.733i Family history of fracture 499 150 (46.2) 97 (55.7) 0.68 (0.47, 0.99) 0.041 0.62 (0.41, 0.95) 0.027 The symptomatic bone phenotype Mandible paine 550 39 (11.0) 6 (3.0) 4.29 (1.73, 10.63) 0.002 3.57 (1.37, 9.28) 0.009 Limb/bone painf 548 41 (11.6) 5 (2.6) 5.16 (1.98, 13.50) 0.001 5.06 (1.84, 13.88) 0.002 Joint pain 535 297 (86.6) 151 (78.6) 1.80 (1.11, 2.91) 0.017 1.04 (0.61, 1.79) 0.873

Skull pain, headaches or migraine 536 46 (13.4) 14 (7.3) 1.99 (1.05, 3.77) 0.036 2.04 (1.03, 4.03) 0.041 Reduced exercise tolerance 543 111 (31.8) 17 (8.8) 5.25 (2.94, 9.37) <0.001 3.30 (1.81, 6.04) <0.001 Abnormal gait 497 75 (23.0) 16 (9.4) 2.90 (1.62, 5.20) <0.001 1.39 (0.73, 2.65) 0.323 OR clustered odds ratio, CI confidence interval, RTA road CX-6258 chemical structure traffic accident aMeans and mean differences given for this continuous variable bIncludes increased bone at sites of tendon and 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 SYN-117 manufacturer ribs/costocartilage 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, camptodactyly, abnormally shaped patellae and pelvis, congenitally short digits, PtdIns(3,4)P2 metacarpals and absent bone in toes cOral 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 dCarpal tunnel syndrome reported or previously operated eExcluding isolated temporomandibular pain fPain within bones, rather than pain within joints

gTwo HBM cases reported sinking in the Dead Sea despite the sea’s high specific gravity hAdjusted for age at recruitment, gender iAdjusted for age at recruitment, gender, years since menopause and oestrogen replacement use Interestingly, HBM cases had increased odds of reporting sinking when trying to swim (Table 4). Further adjustment for body weight, height and history of chronic obstructive pulmonary disease, asthma and smoking (as proxies for lung capacity) did not materially affect this association. Whilst fracture history was no different between cases and controls, HBM cases had reduced odds of reporting a family history of fracture. HBM cases were more likely to report current or Tanespimycin previous experience of pain in their mandible, skull/head (including self-reported migraine) and limb bones in general. Unadjusted results suggested increased odds of joint pain in cases compared with controls; however, this was not apparent after adjustment.