'Sink or swim': an evaluation of the clinical characteristics of individuals with high bone mass

Gregson, C. L., Steel, S. A., O'Rourke, K. P., Allan, K., Ayuk, J., Bhalla, A., Clunie, G., Crabtree, N., Fogelman, I., Goodby, A., Langman, CM, Linton, S, Marriott, E, McCloskey, E, Moss, KE, Palferman, T, Panthakalam, S., Poole, K. E. S., Stone, MD, Turton, J., Wallis, D., Warburton, S., Wass, J., Duncan, E. L., Brown, M. A., Davey-Smith, G. and Tobias, J. H. (2012) 'Sink or swim': an evaluation of the clinical characteristics of individuals with high bone mass. Osteoporosis International, 23 2: 643-654. doi:10.1007/s00198-011-1603-4

Author Gregson, C. L.
Steel, S. A.
O'Rourke, K. P.
Allan, K.
Ayuk, J.
Bhalla, A.
Clunie, G.
Crabtree, N.
Fogelman, I.
Goodby, A.
Langman, CM
Linton, S
Marriott, E
McCloskey, E
Moss, KE
Palferman, T
Panthakalam, S.
Poole, K. E. S.
Stone, MD
Turton, J.
Wallis, D.
Warburton, S.
Wass, J.
Duncan, E. L.
Brown, M. A.
Davey-Smith, G.
Tobias, J. H.
Title 'Sink or swim': an evaluation of the clinical characteristics of individuals with high bone mass
Journal name Osteoporosis International   Check publisher's open access policy
ISSN 0937-941X
Publication date 2012-02
Year available 2011
Sub-type Article (original research)
DOI 10.1007/s00198-011-1603-4
Volume 23
Issue 2
Start page 643
End page 654
Total pages 12
Place of publication Surrey, United Kingdom
Publisher Springer U K
Collection year 2012
Language eng
Formatted abstract
Summary: High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder.
Introduction: High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. Methods: Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex.
Results: Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg/m 2, p < 0.001).
Conclusion: Individuals with unexplained HBM have an excess of clinical characteristics associated with skeletal dysplasia and their relatives are commonly affected, suggesting many may harbour an underlying genetic disorder affecting bone mass.
Keyword Bone mineral density
High bone mass
Negative buoyancy
Skeletal dysplasia
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 1 April 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Health and Rehabilitation Sciences Publications
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 18 times in Thomson Reuters Web of Science Article | Citations
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