Abstract
Osteoporosis is characterised by trabecular bone loss resulting from increased osteoclast activation and unbalanced coupling between resorption and formation, which induces a thinning of trabeculae and trabecular perforations. Bisphosphonates are the frontline therapy for osteoporosis, which act by reducing bone remodelling, and are thought to prevent perforations and maintain microstructure. However, bisphosphonates may oversuppress remodelling resulting in accumulation of microcracks. This paper aims to investigate the effect of bisphosphonate treatment on microstructure and mechanical strength. Assessment of microdamage within the trabecular bone core was performed using synchrotron X-ray micro-CT linked to image analysis software. Bone from bisphosphonate-treated fracture patients exhibited fewer perforations but more numerous and larger microcracks than both fracture and non-fracture controls. Furthermore, bisphosphonate-treated bone demonstrated reduced tensile strength and Young’s Modulus. These findings suggest that bisphosphonate therapy is effective at reducing perforations but may also cause microcrack accumulation, leading to a loss of microstructural integrity and consequently, reduced mechanical strength.
Highlights
Osteoporosis is characterised by a loss of bone mass and can be defined clinically using dual X-ray absorptiometry (DXA) as a T-score less than 2.5 standard deviations below the mean bone mineral density (BMD) in young adults[13,14]
The fracture control group displayed the largest volume of perforations, followed by the bisphosphonate-treated and the non-fracture control group (p = 0.030)
The bisphosphonate-treated group had the highest density of microcracks compared to the fracture and non-fracture control groups, which was statistically significant (p = 0.010) (Fig. 3b)
Summary
Osteoporosis is characterised by a loss of bone mass and can be defined clinically using dual X-ray absorptiometry (DXA) as a T-score less than 2.5 standard deviations below the mean bone mineral density (BMD) in young adults[13,14]. Bone quality refers to the material and structural properties of bone that make it resistant to fracture including bone turnover, collagen and mineral matrix, microarchitecture and accumulated microdamage[6] These factors are all thought to play a significant role in the development of fragility fractures[20,21,22,23] and are relevant for understanding the efficacy of treatment. It has been suggested that bisphosphonate treatment causes an oversuppression of remodeling, resulting in the accumulation of microdamage, which compromises the mechanical properties of bone[43,44] This is evident in both animal and human studies, where concurrent bisphosphonate therapy is associated with microdamage[45,46,47]. The present study aims to investigate the effect of bisphosphonate therapy on trabecular microstructure, including perforations and microcracks, and correlate this with the mechanical strength of bone
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