Objectives

Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls.

Introduction

Bisphosphonates (BP) are the first-line therapy for preventing osteoporotic fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate use is associated with over-suppression of remodeling. Animal studies have reported that BP therapy is associated with accumulation of micro-cracks (Fig. 1) and a reduction in bone mechanical properties, but the effect on humans has not been investigated. Therefore, our aim was to quantify the mechanical strength of bone treated with BP, and correlate this with the microarchitecture and density of micro-damage in comparison with untreated osteoporotic hip-fractured and non-fractured elderly controls.

Osteoporosis is a global health issue with 200 million people suffering worldwide and it is a common condition in the elderly. Bisphosphonates including alendronate and risendronate are considered as the first line treatment for osteoporosis. However, there is increasing evidence that bisphosphonate (BP) therapy is associated with atypical fractures. Animal studies have reported a dose-dependent association between the duration of BP therapy and the accumulation of micro-damage. We tested the hypothesis that hip fracture patients treated with BP exhibited greater micro-damage density than untreated fracture and ‘healthy’ aging non-fracture controls.

Trabecular bone cores from patients treated with BP were compared with patients who had not received any treatment for bone metabolic disease (ethics reference: R13004). Non-fractured cadaveric femora from individuals with no history of bone metabolic disease were used as controls. Cores were imaged in high spatial resolution (∼1.3µm) using Synchrotron X-ray tomography (Diamond Light Source Ltd.) A novel classification system was devised to characterise features of micro-damage in the Synchrotron images: micro-cracks, diffuse damage and perforations. Synchrotron micro-CT stacks were visualised and analysed using ImageJ, Avizo and VGStudio MAX.

Our findings show that the BP group had the highest micro-damage density across all groups. The BP group (7.7/mm³) also exhibited greater micro-crack density than the fracture (4.3/mm³) and non-fracture (4.1/mm³) controls. Furthermore, the BP group (1.9/mm³) demonstrated increased diffuse damage when compared to the fracture (0.3/mm³) and non-fracture (0.8/mm³) controls. In contrast, the BP group (1.9mm³) had fewer perforations than fracture (3.0/mm³) and non-fracture controls (3.9/mm³).

BP inhibits bone remodelling, thereby reducing the number of perforated trabeculae, but over-suppression leads to micro-damage accumulation. Accumulated damage could weaken the trabecular bone in the femoral head and neck, increasing the risk of a fracture during a trip or fall.

An ACL reconstruction is designed to restore the normal knee function and prevent the onset and progression of degenerative changes such as osteoarthritis. However, contemporary literature provides limited consensus on whether knee degeneration can be attenuated by the reconstruction procedure. The aim of this pilot study was to identify the presence of early osteoarthritis after ACL reconstruction using MRI analysis.

19 patients who had undergone an ACL reconstruction (9 isolated ACL rupture, 8 ACL rupture and meniscectomy, 2 ACL rupture and meniscal repair) volunteered for this study. MRI's were collected preoperatively and postoperatively for analysis with a mean follow up of 23 months. The Boston-Leeds Osteoarthritis Knee Score (BLOKS) was used for the analysis of the articular cartilage by a consultant orthopaedic surgeon. Scores ranged from 0–3, with 0 being total coverage and thickness of the cartilage and 3 being no coverage. Qualitative analysis was then conducted on each patient to determine if the articular cartilage improved, degenerated, or did not change between preoperative and follow-up scans.

All patients with isolated ACL rupture were found to either have no change or improved articular cartilage scores in their follow up scans compared preoperatively. In contrast, patients with a meniscal repair displayed worse cartilage scores postoperatively. Lastly, of the patients who had an associated meniscectomy, 6 had worse follow-up results, with the remaining patients showing no change or improved cartilage scores.

The present results indicate that patients with an isolated ACL rupture have a reduced risk of developing OA compared to those with associated meniscal injuries. This has implications for analysing the outcome of current ACL reconstruction techniques and in predicting the likelihood of patients developing OA after ACL reconstruction. Future work will involve confirming this pattern in a larger patient sample, as well as exploring additional factors such as time to surgery delay and rehabilitation strategy.