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

Abstract

SummaryHigh 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.IntroductionHigh 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.MethodsTwo 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.ResultsIndividuals 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/m2, p < 0.001).ConclusionIndividuals 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00198-011-1603-4) contains supplementary material, which is available to authorized users.

Genetics in Endocrinology: Autosomal dominant osteopetrosis revisited: lessons from recent studies

“…Additionally, patients with clinical, not genetically verified, HBM had higher BMI compared with their relatives (205). Thus, these observations suggest that the clinical phenotype of HBM and increased bone mass may also involve fat mass and glucose metabolism.…”

Osteoarthritis and bone mineral density: are strong bones bad for joints?

“…58 It should also be noted that although the HBM cases within this population displayed several clinical features suggestive of a mild skeletal dysplasia, no evidence was found of any significant gait abnormality compared with controls. 56 We speculate that HBM individuals manifest a 'bone-forming' tendency, which contributes to their risk of OA. This is supported by the additional observation that HBM individuals also have a greater prevalence and severity of radiographic pelvic enthesophytes (bony spurs at tendon and ligament insertions).…”

“…56 HBM index cases were initially identified through systematic screening of NHS DXA databases for BMD Z-and/or T-scores X þ 4, excluding scans with artefactual causes of BMD elevation, as previously described. 56 Further HBM cases were subsequently identified through DXA screening of first-degree relatives of index cases, resulting in recruitment of just over 350 cases with unexplained HBM. 56 We recently studied the prevalence and phenotype of OA in this HBM population.…”

“…56 Further HBM cases were subsequently identified through DXA screening of first-degree relatives of index cases, resulting in recruitment of just over 350 cases with unexplained HBM. 56 We recently studied the prevalence and phenotype of OA in this HBM population. HBM individuals were found to have a higher prevalence of self-reported joint replacement and use of nonsteroidal antiinflammatory drugs compared with unaffected family controls, implying an increased risk of OA as ascertained by clinical, as opposed to radiographic, end points.…”

“…59 One caveat is that HBM individuals tend to have a greater BMI, 56 which is well recognised as a risk factor for OA at Osteoarthritis and bone mineral density SA Hardcastle et al a number of sites, particularly the knee. 60 However, although greater BMI appeared to contribute to the association between HBM and knee OA, this association persisted after BMI adjustment, 59 and the relationship between HBM and hip OA appeared to be independent of BMI.…”