Histomorphometric Analysis of Structural and Bone Remodeling Parameters in the Underloaded Ovine Calcaneus

Abstract

Osteoporosis is a disease that affects over three million people in the UK (NHS, 2016), and is categorized by a reduced bone mass leading to decreased bone strength and increased fragility. Clinical features of osteoporotic fractures include increased morbidity (physical impairment, reduced quality of life, pain), greater risk of new fractures and increased mortality (Geusens, 2008). During the lifetime of a typical human, bones are their strongest whilst a person is in their early-mid 20’s. As one ages bone loss begins to occur around the age of 35. One important causal factor leading to osteoporosis is lack of weight-bearing physical activity, which might impact the elderly human population at sites such as the femoral neck resulting in fragility fractures. Around 70,000-75,000 hip fractures occur in the UK each year, additionally every year an increase in incident rates has been observed partly due to an aging population (NHS, 2016). The relationship between a decreased mechanical load and resulting in reduced bone mass is well established. The structural and cellular consequences of mechanical underloading within a temporal animal model are yet to be fully explored. The objective of the current study was to determine the temporal structural changes occurring due to the influence of mechanical under-loading (experienced at day 0/baseline, week 4 and week 16) within an ovine skeletal model. Additionally, this experimental system provided insight into the cellular activity (in terms of bone remodeling) associated with a reduced mechanical loading environment. Within this model by week 16 of mechanical under-loading, an increase in cortical porosity (4%, p=0.017) within the dorsal region and reduced cortical thickness (19.7%, p=0.025) across all combined regions (as well as a regional decrease of 15% and 23% within the medial and ventral regions respectively) was observed. These changes indicating a reduction in bone mass were accompanied by increased cortical remodeling medially (58%;p=0.028) as evidenced by an increase in the proportion (%) of canals undergoing bone formation within that anatomical region. These data demonstrate a reduction in bone mass and increased bone remodeling associated with reduced mechanical load within this skeletal site. Additionally, the data presented here of decreased mechanical load appear to support the observed bone loss and elevated remodeling occurring within the osteoporotic human femoral neck. This investigation,therefore, validates the underloaded ovine calcaneus as a suitable experimental model to investigate the possible pathological events associated with disuse osteoporosis.