Analysis of Body Composition in Individuals With High Bone Mass Reveals a Marked Increase in Fat Mass in Women But Not Men

Abstract

Context:High bone mass (HBM), detected in 0.2% of dual-energy x-ray absorptiometry (DXA) scans, is characterized by raised body mass index, the basis for which is unclear.Objective:To investigate why body mass index is elevated in individuals with HBM, we characterized body composition and examined whether differences could be explained by bone phenotypes, eg, bone mass and/or bone turnover.Design, Setting, and Participants:We conducted a case-control study of 153 cases with unexplained HBM recruited from 4 UK centers by screening 219 088 DXA scans. A total of 138 first-degree relatives (of whom 51 had HBM) and 39 spouses were also recruited. Unaffected individuals served as controls.Main Outcome Measures:We measured fat mass, by DXA, and bone turnover markers.Results:Among women, fat mass was inversely related to age in controls (P = .01), but not in HBM cases (P = .96) in whom mean fat mass was 8.9 [95% CI 4.7, 13.0] kg higher compared with controls (fully adjusted mean difference, P < .001). Increased fat mass in male HBM cases was less marked (gender interaction P = .03). Compared with controls, lean mass was also increased in female HBM cases (by 3.3 [1.2, 5.4] kg; P < .002); however, lean mass increases were less marked than fat mass increases, resulting in 4.5% lower percentage lean mass in HBM cases (P < .001). Osteocalcin was also lower in female HBM cases compared with controls (by 2.8 [0.1, 5.5] μg/L; P = .04). Differences in fat mass were fully attenuated after hip bone mineral density (BMD) adjustment (P = .52) but unchanged after adjustment for bone turnover (P < .001), whereas the greater hip BMD in female HBM cases was minimally attenuated by fat mass adjustment (P < .001).Conclusions:HBM is characterized by a marked increase in fat mass in females, statistically explained by their greater BMD, but not by markers of bone turnover.

Osteoporosis and osteoarthritis

“…In order to eliminate these possible confounders, several studies [35][36][37]38 && ] have used the DXA measurement of L1 in the spine and have adjusted the results for differences in BMI. In patients with HBM, a marked increase in fat mass was found in women, statistically explained by their greater BMD [35].…”

“…In patients with HBM, a marked increase in fat mass was found in women, statistically explained by their greater BMD [35]. HBM is characterized by increased trabecular and cortical BMD and an increased cortical bone area, leading to substantial increase in calculated cortical bone strength [36].…”

High Bone Mass is associated with bone-forming features of osteoarthritis in non-weight bearing joints independent of body mass index

“…Interestingly, HBM individuals also tend to have a greater body mass index (BMI) [12], and women with HBM have elevated fat mass on total body DXA with a particular tendency towards central adiposity [13]. Whilst genetic sequencing is ongoing, HBM cases are thought to have a genetic predisposition to their raised BMD suggesting a causal pathway whereby raised BMD leads to increased fat mass [13], [14].…”

“…Whilst genetic sequencing is ongoing, HBM cases are thought to have a genetic predisposition to their raised BMD suggesting a causal pathway whereby raised BMD leads to increased fat mass [13], [14]. Mouse models have suggested bone turnover directly influences insulin sensitivity and adiposity via a relay involving osteocalcin (an osteoblast-specific protein) and adiponectin (an adipokine produced by white adipose tissue).…”

Bone composition: relationship to bone fragility and anti-osteoporotic drug effects

“…Proteins in the extracellular matrix of bone can also be divided as follows: (a) structural proteins (collagen and fibronectin) and (b) proteins with specialized functions, such as those that (i) regulate collagen fibril diameter, (ii) serve as signaling molecules, (iii) serve as growth factors, (iv) serve as enzymes and (v) have other functions. The relative amount of each of these constituents present in a given bone varies with age, 3 site, 4 gender, 5 ethnicity 6 and health status. 7 The amount, proper arrangement and characteristics of each of these components (quantity and quality) define the properties of bone.…”