Bone Quality: The Determinants of Bone Strength and Fragility

Abstract

Bone fragility is a major health concern, as the increased risk of bone fractures has devastating outcomes in terms of mortality, decreased autonomy, and healthcare costs. Efforts made to address this problem have considerably increased our knowledge about the mechanisms that regulate bone formation and resorption. In particular, we now have a much better understanding of the cellular events that are triggered when bones are mechanically stimulated and how these events can lead to improvements in bone mass. Despite these findings at the molecular level, most exercise intervention studies reveal either no effects or only minor benefits of exercise programs in improving bone mineral density (BMD) in osteoporotic patients. Nevertheless, and despite that BMD is the gold standard for diagnosing osteoporosis, this measure is only able to provide insights regarding the quantity of bone tissue. In this article, we review the complex structure of bone tissue and highlight the concept that its mechanical strength stems from the interaction of several different features. We revisited the available data showing that bone mineralization degree, hydroxyapatite crystal size and heterogeneity, collagen properties, osteocyte density, trabecular and cortical microarchitecture, as well as whole bone geometry, are determinants of bone strength and that each one of these properties may independently contribute to the increased or decreased risk of fracture, even without meaningful changes in aBMD. Based on these findings, we emphasize that while osteoporosis (almost) always causes bone fragility, bone fragility is not always caused just by osteoporosis, as other important variables also play a major role in this etiology. Furthermore, the results of several studies showing compelling data that physical exercise has the potential to improve bone quality and to decrease fracture risk by influencing each one of these determinants are also reviewed. These findings have meaningful clinical repercussions as they emphasize the fact that, even without leading to improvements in BMD, exercise interventions in patients with osteoporosis may be beneficial by improving other determinants of bone strength.

The myokine irisin increases cortical bone mass

“…As a consequence, pMOI, an index of long bone resistance to torsion, and bending strength are significantly increased. Both BMD increases and geometry improvements are known to underlie enhanced bone strength (22)(23)(24). Specifically, by distributing bone mass away from the center, enlarged bone perimeter and cross-sectional area both contribute to increased pMOI and resistance to bending.…”

Towards new material biomarkers for fracture risk

“…However, after reporting a decrease in crystal thickness with age as crystal length increases, Boskey and Mendelson suggested from their preliminary data that mechanical strength is greater when the average crystallinity is greater [68]. Boskey also argued in favour of an optimal situation in which there is a broad distribution of crystal sizes [19] and Fonseca et al reported that bone strength is favoured by greater mineral crystal size heterogeneity [11]. Further, Chachra et al [69] reported that a reduction in crystallite size of bone mineral is associated with a decreased load accommodation and increased fracture risk.…”

“…In contrast, previous studies have shown a decrease in the mineral to organic ratio in ovariectomized animal and osteoporotic human tissue [18,30,33,45,74], suggesting either a lower mineral content and/ or a greater collagen content. The consensus tends to be that in osteoporotic bone, a decrease in mineral content is observed [18,19], resulting in a reduction in mechanical strength [11].…”

“…There are several complex determinants of bone strength and fragility, and although properties which may increase the resistance to one type of mechanical demand, for example static loading, may also be detrimental to other kinds such as fatigue loading [11]. For this reason, material scientists differentiate between stiffness: how well a material resists deformation, toughness: the ability of a material to absorb energy prior to failure and strength: the ability of a material to resist failure when stretched or compressed.…”

Role of Irisin on the bone–muscle functional unit

“…The increase in BMD and the improvement of bone geometrical architecture are recognized parameters used to define high bone quality. [21][22][23] Cross-sectional geometrical properties have been extensively used to measure long bone resistance to axial torsion. Recently, the polar moment of inertia was preferred rather than cross-sectional geometry because it better measures resistance of a long bone to torsion around a particular axis, taking into account the cross-sectional area but also the distribution of bone tissue around the neutral axis.…”