Index cases were asked to pass on study invitations to their firs

Index cases were asked to pass on study invitations to their first-degree ATR inhibitor relatives and spouse/partner(s). These relatives and spouses were invited only once, and non-responders were not followed up. Relatives/spouses with HBM were in turn asked to PF-02341066 supplier pass on study invitations to their (previously

uninvited) first-degree relatives and spouses. Recruitment ran from 1 July 2005 until 30 April 2010. Written informed consent was collected for all in line with the Declaration of Helsinki [21]. Participants were excluded if under 18 years of age, pregnant or unable to provide written informed consent for any reason. This study was approved by the Bath Multi-centre Research Ethics Committee (REC) and at each NHS Local REC. Clinical assessment of HBM characteristics Those index cases, relatives and spouses able to attend their local centre, were clinically assessed by a doctor or research nurse using a standardised structured history and examination questionnaire assessing features previously reported in individuals with sclerosing and/or hyperostotic skeletal dysplasias. Reported operations were coded using OPCS4 (Office of Population, Censuses and Surveys Classification of Surgical Operations and Procedures check details [4th revision]). Joint replacement included OPCS4 codes W37–W58 inclusive. DXA

scans were performed for relatives and spouses after clinical assessment using local Hologic Inc. (Bedford, MA, USA) and GE Lunar Inc. (Madison, WI, USA) DXA systems using each manufacturer’s standard scan and positioning protocols, and DXA weight and routine height measurements were recorded. Manufacturer reference data were used for T- and Z-score calculations (Hologic NHANES and GE Lunar UK reference populations), matched for gender and ethnicity (weight adjustment disabled for GE Lunar scans). BMD was standardised using established formulae [22, 23]. Body mass

index (BMI) was calculated as weight (kilograms)/height (square metres). Serum corrected calcium, phosphate, alkaline phosphatase and a full blood count were analysed at the coordinating centre laboratory (United Bristol Healthcare NHS Trust). Samples delayed in transit for more than Progesterone 48 h were excluded to omit measurement error from haemolysis. All participants had plain radiographs of AP hand and knees, plus AP lumbar spine and pelvis if aged over 40 years. DNA was also collected for future genetic studies, and permission sought for future follow-up. Clinical assessments occurred during a single visit to maximize uniformity. Statistical analysis Descriptive statistics for index cases, relatives and spouses are presented as mean (95% confidence interval (CI)) for continuous and count (percentages) for categorical data and compared using linear regression and chi-squared tests, respectively.

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