Multi-level characterization of human femoral cortices and their underlying osteocyte network reveal trends in quality of young, aged, osteoporotic and antiresorptive-treated bone

The fracture mechanics of human bone: influence of disease and treatment

“…However, experimental studies characterizing the structure of bisphosphonate-treated human cortical bone have found improvements underpinning the general effectiveness of antiresorptive treatments. 57,60 A major limitation of the studies in the literature addressing cortical bone quality in aging and osteoporosis though is the low sample sizes. Future studies characterizing the structure and mechanical properties of clinically diagnosed osteoporosis tissue using age-matched controls are still required to understand the effects of osteoporosis and bisphosphonates on the structure and mechanical properties of cortical bone.…”

“…Although the vast majority of bisphosphonate-related research concerns trabecular bone, the effect of bisphosphonates on cortical bone is now of interest as well due to the site-specific effects of bisphosphonates and the advent of atypical femoral fractures. [55][56][57] Recent studies have highlighted changes to the multi-lengthscale cortical bone structure associated with treatment. Here, we focus on reporting the results from studies investigating human cortical bone, where osteoporosis was diagnosed by osteodensitometry and measurement of the areal bone mineral density with a T-score of o2.5 s.d.s below the reference population signifying osteoporosis as measured by DXA.…”

“…At small length-scales, bisphosphonates have been shown to increase collagen maturity and lower mineral crystallinity in comparison with osteoporotic cortical tissue. 58 In addition, studies on bisphosphonate-treated and osteoporotic cortical bone have revealed a lower degree of mineralization in femoral mid-cortical cross-sections in comparison with young tissue; 57 however, other researchers found in cylindrical cortico-cancellous bone biopsies obtained during fracture repair that bisphosphonate treatment may lead to more homogeneity in the mineralization pattern of the bone structure. 59 These deviances from young tissue and treatment-naive osteoporosis cases indicate that the quality of the cortical bone structure at small length-scales is altered during bisphosphonate treatment in comparison with the osteoporotic tissue.…”

“…57,[60][61][62] The larger osteon sizes and lower amount of Haversian systems, in particular, may have implications for crack propagation and the generation of extrinsic toughness in bone. 63 In the future, studies assessing the mechanical implications of bisphosphonate treatment in human cortical bone are needed, as the atypical fractures associated with long-term use have been hypothesized to be related to the accumulation of fatigue damage.…”

Aging Versus Postmenopausal Osteoporosis: Bone Composition and Maturation Kinetics at Actively-Forming Trabecular Surfaces of Female Subjects Aged 1 to 84 Years

“…(5,6) Bone quality is also dependent on other factors such as homocysteine (which has been proposed as a fracture risk contributor). Moreover, the material compositional properties have been shown to significantly vary as a function of both subject and tissue age, (2,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) and correlate with bone's mechanical properties in both animal models and humans, (8,11,14,16,17) though tissue age was determined on general anatomical morphological criteria (eg, distance from Haversian canal in osteons) rather than more robust, histomorphometric criteria, and most of these studies focused on cortical bone.…”